Millettia ferruginea extract attenuates cisplatin-induced alterations in kidney functioning,DNA damage,oxidative stress,and renal tissue morphology

This study aimed to investigate the beneficial role of Millettia ferruginea extract (MF) in preventing cisplatin (Cisp) induced nephrotoxicity in rats. A total of 55 metabolites were identified using LC-MS analysis. The in vivo results indicated that MF pretreatment for 4 weeks (20 mg/kg b.w.) remarkably attenuated the altered renal biomarkers by decreasing the levels of plasma creatinine, urea, and uric acid when compared to the Cisp-group. The nephroprotective capacity of MF was further strengthened by histopathological observations, where Cisp + MF treated rats showed lower number of inflammatory cells and tubular degenerative changes than the Cisp-group. The harmful effects of cisplatin on renal oxidative stress indicators (MDA, SOD, CAT, and GPx), were restored by the treatment of MF. In addition, the reduction of inflammatory markers (IL-6 and TNF-α), associated with alleviating DNA fragmentation, highlighted the preventive effect of MF in kidney tissue. Additionally, MF components presented lower binding energies when docked into the active site of TNF-α and IL-6. The present findings concluded that M. ferruginea extract exhibited nephroprotective potential, which may be attributed to its antioxidant and anti-inflammatory properties. Further work is recommended to confirm the current results, explore the involved mechanism of action, and determine the therapeutic doses and time.     

Chemical Profile of Lipophilic Fractions of Different Parts of Zizyphus lotus L. by GC-MS and Evaluation of Their Antiproliferative and Antibacterial Activities

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg⁻¹ of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg⁻¹ of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg⁻¹ of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC₅₀) = 4.23 ± 0.18 µg mL⁻¹ of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL⁻¹ of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.     

Malaysian Propolis and Metformin Synergistically Mitigate Kidney Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1β and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin.     

Nephroprotective and antioxidant activities of Salacia oblonga on acetaminophen-induced toxicity in rats

Salacia oblonga, a woody climbing plant belonging to the family Celastaceae, is widely distributed in India and other southeast Asian countries. The genus Salacia have been used particularly for the treatment of diabetes, obesity, gonorrhoea, rheumatism, pruritus and asthma. Acetaminophen (APAP), used as an analgesic drug, produces liver and kidney necrosis in mammals at high doses. The aim of this study was to investigate the nephroprotective and antioxidant activities of the ethanol extract of Salacia oblonga (EESO) at the two dose levels of 250 and 500 mg/kg?bw on APAP-induced toxicity in rats. The results showed that APAP significantly increases the levels of serum urea, creatinine, and reduces levels of uric acid concentration. The EESO reduces these by increasing anti-oxidative responses as assessed by biochemical and histopathological parameters. In conclusion, our results suggest that the EESO possesses nephroprotective and antioxidant effects against APAP-induced nephrotoxicity in rats.     

Nephroprotective Effects of Alhagi camelorum against Cisplatin-Induced Nephrotoxicity in Albino Wistar Rats

Alhagi camelorum (AC) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. The overuse of cisplatin (Cis > 50 mg/m²) is associated with observed nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. Remedial measures are needed for the protection of nephrotoxicity against cisplatin. Thus, we investigated the nephroprotective effects of AC plant extract to prevent cisplatin-induced nephrotoxicity in albino Wistar rats. The presence of polyphenols, phenolic compounds, tannins, and saponins was revealed during phytochemical investigation, and a significantly intense antioxidant activity was recorded. There were no toxicological symptoms in the treated rats, and no anatomical, physiological, or histological abnormalities were found compared to the control rats. The results of correcting cisplatin-induced nephrotoxicity revealed that the extract has a significant ability to treat kidney damage, with most parameters returning to normal after only three weeks of therapy. It is concluded that co-administration of cisplatin with AC extract showed exceptional nephroprotective effects at a dose of 600 mg/kg for Cis-induced nephrotoxicity.     

The effects of strawberry tree (Arbutus unedo L.) water leaf extract and arbutin upon kidney function and primary DNA damage in renal cells of rats

Abstract

Although strawberry tree (Arbutus unedo L.) leaves have long been used as a herbal remedy, insufficient information is available on their nephrotoxicity. We assessed the safety of strawberry tree water leaf extract and its key component arbutin, administered per os to Lewis rats of both genders at 200?mg/kg b.w./day for 14 and 28 days. The effects of the tested compounds on DNA integrity in renal cells was evaluated using alkaline comet assay, while kidney function was studied using serum creatinine and urea levels. Strawberry tree water leaf extract showed high biocompatibility with kidney tissue. It did not impair DNA integrity of renal cells and kidney function, either in male or female rats. However, exposure to single arbutin affected the levels of primary DNA damage in renal cells which could be related to metabolic conversion of arbutin into hydroquinone, whose nephrotoxicity has previously been proven.     

Biosynthesized ZnO Nanoparticles Using Albizia lebbeck Extract Induced Biochemical and Morphological Alterations in Wistar Rats

Nano-based particles synthesized via green routes have a particular structure that is useful in biomedical applications as they provide cheap, eco-friendly, and non-toxic nanoparticles. In the present study, we reported the effect of various concentrations of Zinc oxide nanoparticles synthesized using A. lebbeck stem bark extract (ZnO NPsAL) as stabilizing agent on rat biochemical profiles and tissue morphology. Adult Wistar rats weighing 170 ± 5 g were randomly classified into eight groups of five rats each; Group A served as a control fed with normal diet and water. Groups B1, B2, C1, C2, D1, D2, and E were treated with 40 mg/kg and 80 mg/kg of the 0.01, 0.05, and 0.1 M biosynthesized ZnO NPsAL and zinc nitrate daily by the gavage method, respectively. The rats were anesthetized 24 h after the last treatment, blood samples, kidney, heart, and liver tissues were collected for biochemical and histopathological analysis. The rats mean body weight, serum alkaline phosphatase, alanine aminotransferase, creatinine, urea, bilirubin, protein, albumin, globulin, total cholesterol, triacylglycerol, and high-density lipoprotein were significantly altered with an increased concentration of biosynthesized ZnO NPsAL when compared with the control group (p < 0.05; n ≥ 5). Furthermore, histopathological analysis of treated rats’ kidney, heart, and liver tissue revealed vascular congestion, tubular necrosis, inflammation, and cytoplasmic vacuolation. Biosynthesized ZnO NPsAL showed significant alteration in biochemical parameters and tissue morphology in rats with increasing concentrations of the nanoparticles.     

Terminalia chebula supplementation attenuates cisplatin-induced nephrotoxicity in Wistar rats through modulation of apoptotic pathway

In the present study, we have evaluated the nephroprotective effect of hydroalcoholic extract of Terminalia chebula in cisplatin-induced nephrotoxicity model. Standardised extract was orally administered to Wistar rats for 10 days at different doses. On day 7, 8 mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. T. chebula, in a dose-dependent manner significantly inhibited the elevation of serum creatinine, blood urea nitrogen and oxidant stress markers. The immunohistochemical analysis revealed the increased levels of apoptotic markers and cytokines in cisplatin group were significantly lowered by T. chebula extract. The cisplatin-treated rats kidney showed diffused tubular necrosis and infilteration of inflammatory cells which was reversed in the treatment group. Chemical characterisation of extract by HPLC revealed the presence of corilagin, chebulinic, chebulagic, chebulic, gallic and ellagic acid. The findings of this study discovered that T. chebula ameliorated oxidative and histological damage caused by cisplatin.     

Determination of 12 potential nephrotoxicity biomarkers in rat serum and urine by liquid chromatography with mass spectrometry and its application to renal failure induced by Semen Strychni

In previous nephrotoxicity metabonomic studies, several potential biomarkers were found and evaluated. To investigate the relationship between the nephrotoxicity biomarkers and the therapeutic role of Radix Glycyrrhizae extract on Semen Strychni‐induced renal failure, 12 typical biomarkers are selected and a simple LC–MS method has been developed and validated. Citric acid, guanidinosuccinic acid, taurine, guanidinoacetic acid, uric acid, creatinine, hippuric acid, xanthurenic acid, kynurenic acid, 3‐indoxyl sulfate, indole‐3‐acetic acid, and phenaceturic acid were separated by a Phenomenex Luna C₁₈ column and a methanol/water (5 mM ammonium acetate) gradient program with a runtime of 20 min. The prepared calibration curves showed good linearity with regression coefficients all above 0.9913. The absolute recoveries of analytes from serum and urine were all more than 70.4%. With the developed method, analytes were successfully determined in serum and urine samples within 52 days. Results showed that guanidinosuccinic acid, guanidinoacetic acid, 3‐indoxyl sulfate, and indole‐3‐acetic acid (only in urine) were more sensitive than the conventional renal function markers in evaluating the therapeutic role of Radix Glycyrrhizae extract on Semen Strychni‐induced renal failure. The method could be further used in predicting and monitoring renal failure cause by other reasons in the following researches.     

Anti-hyperalgesic activity of crude extract and 7-methyljuglone of Diospyros lotus roots

This study was designed to evaluate the antihyperalgesic effect of crude extract of Diospyros lotus followed by the isolation and characterisation of 7-methyljuglone in acetic acid and formalin tests. The pretreatment of crude extract evoked dose-dependent inhibition of noxious stimulation with maximum effect of 56.78% in acetic acid-induced writhing test, which were 51.89% and 60.69% in first and second phases, respectively, at 100 mg/kg i.p. The structure of 7-methyljuglone was confirmed by spectroscopic analysis. 7-Methyljuglone evoked profound increase in pain threshhold dose dependently; when it was studied in acetic acid-induced writhing test with 63.73% pain attenuation while 51.22% and 65.44% pain amelioration in first and second phases, respectively, at 100 mg/kg i.p. In conclusion, crude extract and 7-methyljuglone of D. lotus roots possessed both peripheral and central antinociceptive potential and thus could be a useful new therapeutic agent.     

Chemopreventive Effect and HPTLC Fingerprinting Analysis of Jasminum sambac (L.) Ait. Extract Against DLA-Induced Lymphoma in Experimental Animals

The anticancer activity of the ethanolic extract of Jasminum sambac against Dalton’s lymphoma ascites-induced lymphatic cancer in Swiss albino mice was investigated. The anticancer activity of J. sambac was studied against lymphoma using lipid profiles, biochemical parameters, and membrane-bound marker enzymes by standard procedures. A high-performance thin-layer chromatography fingerprinting analysis showed the presence of terpenoids and flavonoids. The levels of cholesterol, triglyceride, VLDL cholesterol, and LDL cholesterol were significantly decreased in tumor-induced mice, while HDL cholesterol showed increased levels compared with those profiles. On treatment with J. sambac, the levels were brought back to near normal. The albumin, creatinine, total protein, urea, and uric acid contents were also approaching normal values. There was s significant increase in the levels of ATPase in group II. These levels were brought back to normal upon plant extract treatment of mice. DNA fragmentation occurred in the tumor-induced group of tissue, and treatment with ethanolic extract reduced the DNA damage caused by lymphoma. Expression of lactate dehydrogenase (LDH) isoenzymes shows an increase in the levels of LDH-4 and LDH-5 in cancer-bearing animals which is brought back to near normal. Histopathological investigation showed normal sections of liver tissues in the treatment group. The results found in mice treated with ethanolic extract 100 mg?kg^?1 body weight quite promising and were comparable with the standard drug 5-fluorouracil. The statistically processed results support the conclusion that the ethanolic extract of J. sambac flower (100 mg?kg^?1) possesses a dose-dependent significant anticancer activity against lymphoma.     

Nephroprotective and antioxidant activities of ethyl acetate fraction of Euphorbia geniculata Ortega family Euphorbiaceae

In continuation of our work on genus Euphorbia, the phytochemical investigation of ethyl acetate fraction of the aerial parts of Euphorbia geniculata Ortega (Eg) family Euphorbiaceae revealed the isolation and identification of eight polyphenolic compounds; gallic acid (1), ellagic acid (2), quercetin-3-O-rutinoside) (rutin) (3), quercetin-3-O-glucopyranoside-7-O-rhamnoside (4), quercetin-3-O-rhamnoside (5), quercetin-3-O-β-D- glucopyranoside (6), and quercetin-3-O-β-D-arabinoside (7) and quercetin (8) using spectrophotometric and physicochemical analysis. Quantitative estimation of total flavonoids and phenolics contents were carried out for total methanolic extract. Biological activities of ethyl acetate fraction including nephroprotective and antioxidant activities were evaluated for the first time. The nephroprotective potential of Eg was evaluated in male rats with thioacetamide induced kidney injury. Antioxidant activity was evaluated using DPPH method.Results; Quantitative estimation of total phenolics and flavonoids content in the total methanolic extract of Eg revealed high phenolics content (285.4 mg GAE /gm extract) in comparison with flavonoids content (36.9 mg RE /gm extract). Isolation and characterization of eight polyphenolic compounds. The nephroprotictive activity was studied using thioacetamide as nephrotoxicant agent resulted in marked nephrotoxicity. While pretreatment of rats with ethyl acetate fraction of Eg significantly attenuated the nephrotoxicity through alteration of kidney biomarkers, improving the redox status of the tissue and so brought the serum biochemical parameters nearly toward the normal levels. The study revealed significant antioxidant activity of Eg in comparison with ascorbic acid. Conclusion; The results suggested that E. geniculata Ortega ethyl acetate fraction could be used in future therapy as nephroprotective and antioxidant drugs of natural source.     

Phytochemical analysis and antidiabetic efficacy of Morus rubra

Morus rubra (red mulberry) is a folk medicine used in management of diabetes. The aim of this article to investigate the antidiabetic activity of hydro alcoholic leaf extracts of Morus rubra in the sprague dawley male rats (SD) model. Authentication of plant material, total Phenolic contents, total flavonoid contents, HPLC analysis, in-vitro antioxidant activity, acute toxicity, in-vivo oral glucose tolerance test, in-vivo STZ induced antidiabetic activity along with biochemical parameters (triglycerides, low-density lipoprotein, high-density lipoprotein, total cholesterol, serum glutamate phosphotransferase, serum glutamate oxaloacetic acid transferase, urea and creatinine). The total phenolic contents 60.32 ​± ​0.80 ​mg/g GAE (gallic acid equivalent) were found higher in ethanolic extract. The total flavonoids 16 ​± ​0.42 ​mg/g QE (quercetin equivalent) were found in petroleum ether extract. M. rubra leaf extracts were tested by HPLC for qualitative and quantitative analysis. 100 ​mg of the dried powder of Morus leaves was dissolve in methanol: water (80:20, v/v) for analysis. Chromatograms of HPLC show the presence of chlorogenic acid 0.55 mg/gm, quercetin 1.90 ​mg/g, isoquercetin 0.68 mg/gm and rutin 0.10 mg/gm. IC₅₀ (Inhibitory concentration) value has been found higher in chloroform extract (92.89 ​μg/ml). Metformin drug is used for positive control, which causes 14.6% improvement in glucose tolerance while M. rubra has been found 11.4. % at the dose of 300 ​mg/kg body wt in normal rats. In STZ treated diabetic rats, it reduces 13.0% blood glucose level while metformin reduces 21.9% up to dosing level of 300 ​mg/kg body wt. It produces reduction in biochemical parameters like, total cholesterol (TC), triglycerides (TG), SGPT, LDL, urea, creatinine and SGOT while HDL has been increased. Results show the hydro-alcoholic leaves extract of Morus rubra exhibited antidiabetic, antioxidant and hypolipidemic properties. This suggests that M. rubra has great potential to develop novel antidiabetic drug to manage this disastrous disease.     

Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K/AKT Signaling Pathway

Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg/kg body weight (b.w.)/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg/kg b.w./day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg/kg b.w./day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman–Keul’s test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K/AKT signaling pathways.     

Effect of ethanol extract of Sphaeranthus indicus on cisplatin-induced nephrotoxicity in rats

Cisplatin is an anticancer drug extensively used against a variety of cancers. Cisplatin chemotherapy is found to manifest dose-dependent nephrotoxicity. Depletion of the renal antioxidant defence system has been suggested to be the main cause of cisplatin-induced nephrotoxicity. The purpose of this study is to investigate whether the ethanol extract of entire plant of Sphaeranthus indicus could reduce the intensity of toxicity in albino rats. Nephrotoxicity was assessed by determining the serum creatinine and urea levels and renal antioxidant status in rats after cisplatin administration (12?mg?kg(-1)?body weight, i.p.). The ethanol extract of S. indicus (150 and 300?mg?kg(-1)?body weight) was administered orally from the sixth day onwards for 10 days after cisplatin administration. The extract significantly reduced the elevated serum creatinine and urea levels. Renal antioxidant defence systems, such as superoxide dismutase, catalase, glutathione peroxidase activities and reduced glutathione level that are depleted by cisplatin therapy were restored to normal by treatment with the extract. Cisplatin-induced lipid peroxidation was also found to be markedly reduced by treatment with the extract. These results suggest that S. indicus has protective effect against cisplatin-induced nephrotoxicity, which may be attributed to its antioxidant potential.     

Chemical Analysis of Eruca sativa Ethanolic Extract and Its Effects on Hyperuricaemia

In vivo assays and chemical analyses were performed on the ethanolic extract from leaves of Eruca sativa. UHPLC-ESI-QTOF analysis confirmed the presence of glucosinolates and flavonol glucosides. The major flavonoid of the ethanolic extract, kaempferol-3,4′-di-O-β-glucoside, was isolated, a HPLC-DAD method developed and validated to quantify its content in the extract. In vivo experiments were carried out on Wistar rats with hyperuricaemia induced by potassium oxonate and uric acid. A hypouricaemic effect was observed in hyperuricaemic Wistar rats treated with ethanolic extract at dose of 125 mg/kg and kaempferol-3,4′-di-O-β-glucoside at dose of 10 mg/kg. The main anti-hyperuricaemic mechanism observed in the extract was uricosuric. Kaempferol-3,4′-di-O-β-glucoside was identified as an important component responsible for the total activity of the ethanolic extract and was considered as a good chemical and biological marker of the ethanolic extract of E. sativa. The obtained results indicated the potential of E. sativa in the treatment of hyperuricaemia and its comorbidities.     

Efficacy of Ficus spp. on renal injury induced by hypercholesterolaemia

The ethanol and hexane extracts of Ficus microcarpa, Ficus religiosa and Ficus mysorensis leaves were evaluated against renal injury induced by hypercholesterolaemia. Phytochemical screening of the investigated plants was undertaken. For the in vivo study, all rats were orally given cholesterol (30?mg?kg?1 body weight, BW) and leaves extract (500?mg?kg?1 BW) five times per week for 9 weeks. Hypercholesterolaemic rats showed significant increases in urea nitrogen and creatinine while serum protein and albumin levels, nitric oxide (NO), Na?-K?-ATPase and phospholipids in kidney tissue were all decreased. Treatment with leaves extract improved kidney function indices (urea nitrogen, creatinine, serum protein and albumin), kidney disorder biochemical parameters (NO, Na?-K?-ATPase and phospholipids), haematological profile (haemoglobin, RBCs and WBCs) and kidney histopathology. In conclusion, Ficus spp. succeeded in improving renal injury induced by hypercholesterolaemia, with the most potent effects seen while using Ficus microcarpa hexane extract.     

CE Determination of Creatinine and Uric Acid in Saliva and Urine During Exercise

A simple and reliable method based on capillary electrophoresis with electrochemical detection (CE–ED) was applied to study the effect of aerobic exercises on creatinine and uric acid concertration in saliva and urine. The pH value, the running buffer concentration, the SDS concentration, separation voltage, injection time and the potential applied to the working electrode were investigated to find the optimum conditions. The detection limits (S/N = 3) for creatinine and uric acid were 3.6 μmol L^?1 and 0.86 μmol L^?1, respectively. This method was successfully used in the rapid analysis of creatinine and uric acid in saliva samples. After aerobic exercises, creatinine concentration decreased, and uric acid concentration increased in saliva. In urine, the concentrations of creatinine and uric acid both increased after exercise.     

A novel preventive mechanism of gentamicin‐induced nephrotoxicity by atorvastatin

Atorvastatin (ATO) inhibits the synthesis of nonsteroidal isoprenoid compounds and possesses a pleiotropic effect. However, the detailed mechanism of ATO in preventing gentamicin (GM)‐induced renal injury remains obscure. Although underlying multifaceted mechanisms involving GM‐induced nephrotoxicity were well known, further work on elucidating the essential mechanism was needed. Using a fluorogenic derivatization–liquid chromatography tandem mass spectrometry proteomic method (FD‐LC–MS/MS method), we investigated the effects and mechanisms of ATO treatment on GM‐induced nephrotoxicity in rats. Consequently, 49 differentially expressed proteins were identified. The most significant mechanisms of nephrotoxicity caused by GM were mitochondrial dysfunction, fatty acid metabolism and oxidative stress. Their upstream regulator was found to be PPARα. The proteins involved in GM nephrotoxicity were sodium–hydrogen exchanger regulatory factor (SLC9A3R1), cathepsin V (CTSV), macrophage migration inhibitory factor (MIF) and RhoGDP dissociation inhibitor alpha (ARHGDIA). After ATO intervention, we observed a reversed enrichment pattern of their expression, especially in CTSV and SLC9A3R1 (P‐value<0.05). We predicted that ATO may improve abnormal phospholipid metabolism and phospholipidosis caused by GM and also alleviate cell volume homeostasis and reverse the interference of GM with the transporter. Furthermore, proteomic results also provided clues as to GM‐induced nephrotoxicity biomarkers such as CTSV and transthyretin.     

Chromatographic Properties of Ethanol/Water Mobile Phases on Silica Based Monolithic C18

A simple and reliable method based on capillary electrophoresis with electrochemical detection (CE–ED) was applied to study the effect of aerobic exercises on creatinine and uric acid concertration in saliva and urine. The pH value, the running buffer concentration, the SDS concentration, separation voltage, injection time and the potential applied to the working electrode were investigated to find the optimum conditions. The detection limits (S/N = 3) for creatinine and uric acid were 3.6 μmol L⁻¹ and 0.86 μmol L⁻¹, respectively. This method was successfully used in the rapid analysis of creatinine and uric acid in saliva samples. After aerobic exercises, creatinine concentration decreased, and uric acid concentration increased in saliva. In urine, the concentrations of creatinine and uric acid both increased after exercise.