Gentamicin-induced Nephrotoxicity Research Articles

Renoprotective Effects of Valsartan And Amlodipine in a Nephrotoxic Model of Experimental Animals

Background: Calcium channel blockers and AT1 antagonists have efficacious effects to control elevated blood pressure by different mechanisms. They are used widely in co-morbid hypertensive patients either to prevent deterioration of blood pressure or to protect the cardiovascular diseases from further progression. Objectives: This work aims to investigate the protective effects of valsartan and amlodipine against gentamicin-induced nephrotoxicity in experimental animals. Methods: Twenty-four rabbits were divided randomly into four groups, each of six animals. The first group was kept as the normal control group. Second, third and fourth groups were taken as a nephrotoxic model by giving gentamicin (80mg/kg IP) for 7 days. Blood samples were collected to investigate the kidney biomarkers including serum creatinine, BUN, Crcl, uric acid and potassium level. Urine collection was done to measure pH, volume as well as urine creatinine. Bodyweight was measured before and after treatment, furthermore, the weights of heart and kidneys were done at the end of the study. Results: The outcomes of this study showed a significant elevation in all kidney biomarkers in a nephrotoxic-induced group accompanied by the reduction in the weights of heart and kidney as compared with the control one. The treated groups either valsartan or amlodipine showed little improvements in some parameters compared with the nephrotoxic-induced group. Conclusion: From the results of the present study, it was suggested that both medications might have renoprotective effects that obviously reduced the kidney biomarkers as well as there was no significant difference between the two drugs concerning their protective effect.

Toll-like receptor-2 mediates systemic inflammation in gentamicin-induced rat nephrotoxicity.

Gentamicin is an aminoglycoside antibiotic commonly administrated to patients with Gram-negative infections. Gentamicin induced nephrotoxicity by functional and structural impairment. Toll-like receptors (TLRs) as key mediators in the innate and adaptive immune system response involved in gentamicin-induced nephrotoxicity. The present study aimed to investigate the gene expression of TLR2 and pro-inflammatory cytokines in the renal tissues and buffy coat of the whole blood in gentamicin-treated rats. Twenty adult male Sprague Dawley rats weighing 180-200 were randomly divided into gentamicin (100mg/kg, i.p) and control groups (n=10). After 10days, the serum creatinine (Cr) levels and blood urea nitrogen (BUN) were measured. The mRNA levels of TLR2, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and monocyte chemoattractant peptide (MCP)-1 were investigated in the renal tissue and buffy coat by qRT-PCR. Kidney histological analysis performed by hematoxylin-eosin (H&E) staining. Functional disturbance is characterized by a significant increase in the serum levels of Cr and BUN in the gentamicin group. Renal tissue slides of the gentamicin group indicated severe glomerular and tubular damage including lobulation of the glomerular tuft, Bowman's space enlargement, acute tubular necrosis, and proximal tubular destruction. The mRNA levels of IL-1β, TNF-α, MCP-1, and TLR2 increased in the buffy coat, but all of them except TLR2 decreased in the renal tissues in the gentamicin group compared with controls. Gentamicin administration induced relative systemic inflammation, which may be related to an increase in the mRNA levels of TLR2 results in gene expression of pro-inflammatory chemokines and cytokines including IL-1β, TNF-α, and MCP-1 in immune cells.

Nephroprotective effect of ferulic acid on gentamicin-induced nephrotoxicity in female rats

Ferulic acid is a kind of phenolic compound that can be found in various fruits and vegetables. This study aims to investigate the effect of ferulic acid on nephrotoxicity induced by gentamicin (GM). In this study, rats were separated into 4 groups such that each containing 8 randomly selected rats: Control group, Ferulic Acid (FA) group, Gentamicin (GM) group and Gentamicin + Ferulic acid (GM + FA) group. Blood samples were collected after 24 hours following the 8-day trial period, and kidneys were taken out for histopathological evaluation. Serum urea, creatinine, uric acid and LDH analyses were performed in autoanalyzer while Malondialdehyde (MDA), Advanced Oxidized Protein Products (AOPP), Glutathione (GSH), Superoxide dismutase (SOD), Catalase (CAT), Interleukin 6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) analyses were performed in ELISA, and kidney tissues were also examined histopathologically. Urea (p < .001), creatinine (p < .001), MDA (p < .01), AOPP (p < .001), IL-6 (p < .01) and TNF-α (p < .001) levels were found to be statistically and significantly lowered in GM + FA group when compared to GM group. As a result, ferulic acid has reduced the inflammation in nephrotoxicity induced by GM, causing decreased oxidative stress. In this study, anti-inflammatory features of ferulic acid have come to the forefront rather than the antioxidant features. It can be said that ferulic acid reduces nephrotoxic damage and has protective properties for kidneys.

Extracts from Commelina diffusa Protect Against Gentamicin-Induced Nephrotoxicity in Wistar Rats

Extracts from Commelina diffusa Protect Against Gentamicin-Induced Nephrotoxicity in Wistar Rats

Androgen/androgen receptor affects gentamicin-induced nephrotoxicity through regulation of megalin expression

AimInvestigation whether androgen/androgen receptor (AR) might regulate megalin expression and/or functionality and thus affecting Gentamicin-induced nephrotoxicity (GIN). Main methodsMale Wistar rats were treated with gentamicin with/out AR ligands (testosterone as agonist and flutamide as antagonist). Megalin expression in the kidney tissues was determined by real-time RT-PCR and western blot. Besides, megalin functionality was assessed using immunofluorescence imaging of fluorescein isothiocyanate (FITC) conjugated bovine serum albumin (BSA) (FITC-BSA). The effects of different treatments on the kidney were assessed at the structural level by histopathological evaluation and the biochemical level by colorimetric assay of blood urea nitrogen (BUN), serum creatinine (SCr) and urinary albumin/creatinine (A/C) ratio, besides, kidney expression of neutrophil gelatinase-associated lipocalin (NGAL) by immunoblotting. Key findingsOur results revealed that treatment with testosterone either alone or combined with gentamicin increased megalin expression at mRNA and protein levels as well as at the functional level. These effects were paralleled by increased GIN as manifested by increased SCr, BUN, A/C ratio, renal expression of NGAL or histopathological changes. On the other hand, treatment with flutamide ameliorated GIN and megalin expression and functionality. Computational analysis of megalin promotor revealed the presence of multiple response elements that mediate androgen response. SignificanceAndrogen/AR regulates megalin expression at the transcriptional level and consequently GIN. This may explain the sexual dimorphism in GIN and might represent a druggable target for treatment or prevention of GIN.

Effects of Quercetin and Coenzyme Q10 on gentamicin-induced nephrotoxicity in rats

Purpose: We investigated the effects of Quercetin and Coenzyme Q10 antioxidant, on gentamicin-induced renal failure in rats. Materials and Methods: The rats were given gentamicin (100 mg/kg/day, i.m., once a day), gentamicin (100 mg/kg/day, i.m.once a day) + Quercetin (15 mg/kg i.p. once a day) and gentamicin (100 mg/kg/day, i.m.) + Coenzyme Q10 (8 mg/kg i.m. once a day). Results: In control the BUN value was 26.8 ± 0.8 (mg/100 mL); whereas, it was 117.3 ± 15.4 in gentamicin group. Renal histopathologic examination confirmed acute tubular necrosis in this group. In rats treated with gentamicin + Quercetin and gentamicin + Coenzyme Q10, a partial improvement in biochemical and histologic parameters was observed. BUN values were 117.3 ± 15.4, 44.0 ± 8.3, 47.8 ± 13.8 in gentamicin, gentamicin plus Quercetin and gentamicin plus Coenzyme Q10 treated groups, respectively. Creatinine values were 4.3 ± 0.6, 0.8 ± 0.1, 1.5 ± 0.4 in gentamicin, gentamicin plus Quercetin and gentamicin plus Coenzyme Q10 treated groups, respectively. Conclusion: These results suggest that the administration of Quercetin and Coenzyme Q10 may have a protective effect on gentamicin-induced nephrotoxicity in rats.

Nephroprotective Effects of Cinnamon and/or Parsley Oils against Gentamicin-Induced Nephrotoxicity in Rats

Nephroprotective Effects of Cinnamon and/or Parsley Oils against Gentamicin-Induced Nephrotoxicity in Rats

The effect of aryl hydrocarbon receptor ligands on gentamicin-induced nephrotoxicity in rats.

Polycyclic aromatic hydrocarbons (PAHs)/aryl hydrocarbon receptor (AhR) regulate the expression of target genes, including drug transporter genes which harbor xenobiotic response element (XRE) in their promoter regions. Thus, PAHs/AhR could alter the toxicokinetic profile of many nephrotoxic drugs, including aminoglycosides. In the current study, we investigated the expression and localization of AhR and megalin in rat kidney. Furthermore, we investigated whether AhR and its ligands could modulate the expression of megalin and consequently the gentamicin-induced nephrotoxicity (GN) in rats. Both megalin and AhR receptors are expressed in the proximal tubules of the rat kidney. Treatment with AhR agonist benzo(a)pyrene aggravated GN as indicated by a significant increase in serum creatinine, BUN, KIM1, NAGL, CD-86, and urinary albumin/creatinine ratio. On the other hand, treatment with AhR antagonist resveratrol ameliorated GN as manifested by a pronounced decrease in the aforementioned parameters. The effects of AhR ligands on GN were associated with altered expression of megalin receptor.

Protective Effect of Celastrol on Gentamicin-induced Nephrotoxicity in Mice

Protective Effect of Celastrol on Gentamicin-induced Nephrotoxicity in Mice

Royal Jelly and Aliskiren mutually annul their protective effects against gentamicin-induced nephrotoxicity in rats

Background and Aim:Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained because of its nephrotoxic potential. Royal jelly (RJ) and aliskiren (ALK) can individually prevent such toxic effects. The aim of this study was to explore the protective effects of a combination treatment of RJ and ALK on GM-mediated nephrotoxicity.Materials and Methods:Thirty-two adult female. Wistar rats were divided equally into four groups: (I) Receiving normal saline; (II) GM (100 mg/kg, intraperitoneal [i.p.] injection); GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection); and (IV) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection) in combination with RJ (150 mg/kg, orally). All treatments were administered daily for 10 days. The blood levels of creatinine, urea, uric acid, albumin, and total protein were measured. Then, the animals were sacrificed, and the kidneys were taken for histopathology.Results:Compared to normal control rats, GM-injected rats showed significantly (p<0.001) higher serum concentrations of uric acid, urea, and creatinine as well as evidently (p<0.001) lower blood levels of albumin and total protein. Moreover, GM administration was associated with significant renal histopathological changes. All these alterations were considerably (p<0.05) improved in GM-injected rats receiving ALK compared to rats receiving GM alone. However, when RJ was given in combination with ALK to GM-injected rats, it lessened the beneficial nephroprotective effects of both agents.Conclusion:The combination treatment of RJ and ALK is not desirable for GM-induced nephrotoxicity. Further studies are crucial to accurately explore the precise mechanism of RJ antagonistic interaction with ALK.

Irbesartan Attenuates Gentamicin-induced Nephrotoxicity in Rats through Modulation of Oxidative Stress and Endogenous Antioxidant Capacity.

Background:Overproduction of reactive oxygen species and free radicals is the main mechanism beyond gentamicin-induced nephrotoxicity. Irbesartan and other angiotensin II blockers offer significant nephroprotective effect through improvement of renal function and reduction of renal inflammation. Therefore, the objective of this study was to illustrate the nephroprotective effect of irbesartan in rats regarding the oxidative stress of irbesartan biomarkers.Methods:Thirty male Sprague–Dawley rats were used; they were divided into three groups: Group I (10 rats) treated with distilled water, Group II (10 rats) treated with gentamicin, and Group III (10 rats) treated with gentamicin plus irbesartan for 12 days. Blood urea, serum creatinine, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GSH), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule (KIM-1), and cystatin-c were measured in each group.Results:Irbesartan significantly reduced blood urea, serum creatinine, serum MDA, NGAL, KIM-1, and cystatin-c [P < 0.05]. Irbesartan significantly increases SOD [P < 0.05] without significant effect in elevation of GSH serum levels.Conclusions:This study concluded that irbesartan has a nephroprotective effect in attenuation of acute nephrotoxicity through modulation of oxidative stress and antioxidant capacity in rats.

Protective effect of Cupressus macrocarpa and Dioon edule against gentamicin-induced nephrotoxicity in rats

Context: It has been reported that Cupressus macrocarpa Hartw. ex Gordon (Cupressaceae) and Dioon edule Lindl. (Zamiaceae) contain compounds with antioxidant and anti-inflammatory effects; therefore, they may exert a nephroprotective effect. Aims: To explore the renoprotective effect of C. macrocarpa and D. edule and the underlying molecular mechanisms. Methods: Ten male Wister rats were used for each group of control (1% CMC in saline), gentamicin (GM, 40 mg/kg), D. edule leaves methanol extract (DLM), C. macrocarpa leaves combined petroleum ether and methanol extract (CLEM) and C. macrocarpa roots methanol extract (CRM). Rats were orally administered the extracts (250 mg/kg) daily concomitantly for 9 days with GM. Evaluation of kidney function, histopathology and measuring renal AMPK-α1, NF-κB and iNOS genes expression were carried out. There were no symptoms of systemic adverse effects in any treated group. Results: Blood urea nitrogen (mg/dL) was significantly reduced by CLEM (24.0 ± 1.205) and CRM (22.889 ± 1.250). Creatinine (mg/dL) was significantly decreased by CLEM (0.59 ± 0.022) and CRM (0.580 ± 0.029). Gene expression of AMPK-α1 enhanced by CLEM (16.717 ± 0.430), CRM (19.18 ± 0.871), DLM (0.417 ± 0.020). iNOS was downregulated by CLEM (0.9 ± 0.056), CRM (1.53 ± 0.044), and DLM (1.642 ± 0.050). NF-κB was decreased by CLEM (1.148 ± 0.076), CRM (0.918 ± 0.065), and DLM (1.783 ± 0.071). CRM and CLEM exhibited normal to mild renal degeneration and mild to moderate expression of iNOS. Conclusions: C. macrocarpa extracts exhibited significant renoprotective effect and could be considered as a new promising strategy against renal complications.

Zaštitni efekti zelenog čaja i borovnice na gentamicinom uzrokovanu nefrotoksičnost kod pacova

The aim of our study was to investigate if green tea and bilberry have protective effect on gentamicin-induced kidney damage, when applied together, and to make a connection between their effects. GM group of rats received only gentamicin, GT group received green tea only, B group received only bilberry, whereas control (C) group received saline only. GT+GM group received green tea together with gentamicin, and B+GM group received bilberry together with gentamicin. Biochemical analysis showed significantly increased urea and creatinine levels in GM group when compared to groups that also received bilberry or green tea. Histological analysis showed complete disruption of glomerular basal membrane as well as basal membranes of both proximal and distal tubules in GM group. These destructive effects were significantly milder and limited only to proximal tubules when bilberry or green tea was applied simultaneously with gentamicin. Both green tea and bilberry protective effect on gentamicin-induced nephrotoxicity is manifested because of their strong antioxidant activity. Since they are strong antioxidants, widely distributed in nature, they can offer available and inexpensive adjuvant therapy in Gram-negative infections, which can relieve gentamicin nephrotoxicity, but will not affect its bactericidal effect.

Repeated administration of fluvoxamine worsens gentamicin-induced nephrotoxicity in rats

Background: Depression is one of the most prevalent and life-threatening forms of mental disorders in chronic kidney disease. Antidepressant agents such as fluvoxamine are broadly prescribed in this situation. This study investigated the effects of fluvoxamine on gentamicin (GEN)-induced nephrotoxicity in rats. Materials and Methods: Twenty-four male Wistar rats were randomly divided into four groups (n = 6) including (1) control group, (2) GEN group, (3) GEN + fluvoxamine (25 mg/kg) group, and (4) GEN + fluvoxamine (50 mg/kg) group. Fluvoxamine was orally given to animals 45 min before GEN was injected (100 mg/kg, intraperitoneally [i.p.]). Blood urea nitrogen (BUN), creatinine (Cr), sodium (Na+), potassium (K+), and malondialdehyde (MDA) levels in serum were measured. Moreover, the glucose (Glu) and protein (Pro) levels in urine and the ratio of kidney to body weight (g/100g body weight) were determined. Histopathological alterations in kidney were evaluated. Results: GEN significantly increased the Cr and BUN serum levels as well as urine Glu and Pro concentrations (P ≤ 0.001). Fluvoxamine exacerbated the elevation in the indicated parameters. GEN also significantly increased the serum MDA levels. Fluvoxamine had no effect on the elevated serum levels of MDA. GEN did not show any effect on the K+ and Na+ serum concentrations. Increased kidney-to-body weight ratio due to GEN nephrotoxicity was further exacerbated by 25 mg/kg of fluvoxamine (P ≤ 0.001). Pathologic findings also confirm the biochemical results. Conclusion: The data suggest that fluvoxamine worsens the nephrotoxicity of GEN. However, further clinical and animal investigations are required to elucidate the mechanism of this interaction.

Identification of urinary microRNA biomarkers for in vivo gentamicin-induced nephrotoxicity models.

BackgroundAlthough previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers.ObjectivesIn this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity.MethodsFor this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats.ResultsGEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein.ConclusionsThese results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

Renoprotective effect of Lycopene on Renal Functional and Histopathological changes in Gentamycin Induced Nephrotoxicity in Rats.

Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on renal function. There are various forms, and some drugs may affect renal function in more than one way. Nephrotoxins are substances displaying nephrotoxicity. The aim of this study is to explore the effect of lycopene inhibition in lesions of gentamicin-induced nephrotoxicity, Mature 24 male mature Sprague-Dawley rats were divided into 4 groups of 6, group1: control, group 2 sham received daily lycopene injection (200 mg/kg) for 12 days, group 3 received daily GS injection (100mg/kg) for 12 days, group 4 received daily GS (100 mg/kg) and lycopene injection (100mg/kg)) for 12 days. After 12 days, rats were anaesthetized, blood sample were obtained and kidneys were removed then stained with hematoxylin and eosin method and then were studied histophatologically. Serum creatinine and urea were measured. lycopene significantly decreased the levels of urea and creatinine in treated group compared with the nephrotoxic untreated group. treatment of nephrotoxic animals with lycopene could significantly inhibit leukocyte infiltration and tubular necrosis in comparison with the nephrotoxic untreated group the findings showed that lycopene alleviates loss of leukocyte infiltration and tubular necrosis and exerts beneficial effects on kidney function test in nephrotoxic group

Development of a Novel Pharmaceutical Formula of Nanoparticle Lipid Carriers of Gentamicin/α-Tocopherol and In Vivo Assessment of the Antioxidant Protective Effect of α-Tocopherol in Gentamicin-Induced Nephrotoxicity

Gentamicin is a potent antibiotic with a nephrotoxicity drawback which limits its use. D-α-tocopherol polyethylene glycol succinate (α-tocopherol) is widely used as a surfactant and have potent antioxidant properties. This study aimed to assess the protective effect of α-tocopherol on gentamicin-induced nephrotoxicity by loading gentamicin on nanostructured lipid carriers (NLC). In vivo, the product was administered intravenously to three groups of rabbits (control, gentamicin and gentamicin/α-tocopherol NLC) for 10 consecutive days. Blood was collected on days 1, 5 and 10 to assess renal function. A significant difference in all plasma parameters related to kidney function were observed in the gentamicin group compared to the control by day 5 and 10, confirming the nephrotoxicity effect. On the other hand, the same parameter levels of the NLC group were significantly different compared to the gentamicin group, confirming the protective effect on kidney function. Gentamicin also caused significant decreases in plasma levels of glutathione sulfhydryl (GSH) and superoxide dismutase (SOD) activity. However, gentamicin-α-tocopherol NLC significantly elevates both plasma levels of GSH as well as SOD activity. The present work indicates that, loading of gentamicin on NLC by using α-tocopherol, is an innovative strategy to protect against aminoglycoside-induced nephrotoxicity due to its antioxidant activity.

The protective role of estrogen and its receptors in gentamicin-induced acute kidney injury in rats

AimInvestigating the impact of 17β-Estradiol/estrogen receptors in gentamicin-induced nephrotoxicity. Main methodsThree weeks post-ovariectomy or sham surgery for the Wistar albino female rats, thirty sham rats were randomly grouped (n = 6), received either vehicle or gentamicin; the estrogen receptors down regulator (fulvestrant); gentamicin plus fulvestrant; gentamicin plus the phytoestrogen (genistein). Forty–eight ovariectomized rats were randomly grouped (n = 6), treated with either vehicle or gentamicin; fulvestrant; gentamicin plus fulvestrant; genistein; gentamicin plus genistein; estradiol benzoate; gentamicin plus estradiol benzoate. Just post-treatment termination, the traditional kidney injury biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers (serum Kidney injury molecule −1, cystatin C, lactate dehydrogenase and, gamma-glutamyl transferase) were determined. Bovine serum albumin labeled with fluorescence isothiocyanate assessed megalin expression/endocytic functionality in the proximal tubules epithelial cells (PTECs). The immunohistochemical investigation for the same-sectioned slides of PTECs assessed the correlation between estrogen receptors α and megalin receptors expression. Histopathological examination of PTECs and subjective scoring system graded the damage markers. Key findingsEstrogen receptor α expression was markedly dimensioned post-ovariectomy, co-localized and inversely correlated to megalin expression. Serum levels of the novel biomarkers were directly proportional to megalin expression in the PTECs and inversely correlated with estrogen receptor α expression. The injury was exaggerated in ovariectomized and intact rats received fulvestrant. Supplementation with estrogen or genistein ameliorated this injury. SignificanceEstrogen/estrogen receptors have a protective impact on gentamicin-induced acute kidney injury. Estrogen receptors antagonist exacerbate the injury, and oppositely, estrogens or phytoestrogens improve it.

N-Acetylcysteine Ameliorates Gentamicin-Induced Nephrotoxicity by Enhancing Autophagy and Reducing Oxidative Damage in Miniature Pigs.

ABSTRACTThe clinical use of gentamicin over prolonged periods is limited because of dose and time-dependent nephrotoxicity, in which intracellular oxidative stress and heightened inflammation have been implicated. Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. The aim of this study was to determine changes in autophagy in response to the antioxidant N-acetylcysteine (NAC), via its effects on oxidative stress, inflammation, apoptosis, and renal function, following treatment with gentamicin in mini pigs. Adult mini pigs were divided into isotonic saline solution, gentamicin, and gentamicin plus NAC combination treatment groups. Gentamicin-induced histopathological changes, including inflammatory cell infiltration and tubular necrosis, were attenuated by NAC. NAC ameliorated the gentamicin-induced decreases in the levels of autophagy-related proteins, such as LC3 (microtubule-associated protein 1 light chain 3), PINK1 (phosphatase and tensin homologue deleted on chromosome10-induced kinase 1), phospho-parkin, AMBRA1 (activatingmolecule in Beclin 1-regulated autophagy), p62/SQSTM1 (sequestosome protein 1), and polyubiquitinated protein aggregates. NAC also caused a significant reduction in oxidative damage markers, including 4-hydroxy-2-nonenal, protein carbonyls, γ-H2AX (gamma histone variant H2AX), and 8-hydroxy-2′-deoxyguanosine, in gentamicin-treated animals. These data show that the protective effects of NAC might be related, at least in part, to a reduced inflammatory response, as observed in animals treated with both gentamicin and NAC. These results suggest that autophagy could be a new therapeutic target for preventing gentamicin-induced kidney injury, and that NAC might ameliorate gentamicin-induced nephrotoxicity by autophagy.

Antioxidant, anti-inflammatory, and antiapoptotic effects of virgin coconut oil against antibiotic drug gentamicin-induced nephrotoxicity via the suppression of oxidative stress and modulation of iNOS/NF-ĸB/caspase-3 signaling pathway in Wistar rats.

Gentamicin is an effective antibiotic against severe infections; however, its major side effect is oxidative nephrotoxicity. We explored whether virgin coconut oil (VCO) could mitigate gentamicin-induced nephrotoxicity. Rats were fed with VCO-supplemented diet for 16 days against renal toxicity induced by gentamicin (100mg/kg bw, ip) from Day 11 to 16. Gentamicin caused marked elevated serum urea, uric acid, and creatinine levels, followed by considerable depletion in renal antioxidant enzymes, glutathione (GSH), while the malondialdehyde (MDA) level increased significantly. It significantly increased renal cytokines and nitric oxide (NO) levels, confirmed by renal histopathology. The expression of inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-ĸB), and caspase-3 was prominently increased. VCO-supplemented diet significantly modulated the levels of biochemical indices, downregulated the expression of NO, iNOS, NF-ĸB, caspase-3, cytokines, and alleviated histopathological lesions. VCO protects against gentamicin-induced nephrotoxicity; thus, it could be a promising dietary supplement for patients undergoing gentamicin treatment. PRACTICAL APPLICATIONS: Gentamicin is an efficacious clinical antibiotic used against severe infections; however, the robust body of evidence indicates that the nephrotoxic side effect constrained its use. Virgin coconut oil (VCO) is an edible oil with growing human consumption and pharmacological effects. Our study has reported herein, for the first time, that VCO diet prevented the nephrotoxicity of gentamicin. Dietary supplementation of this oil could be beneficial in alleviating the nephrotoxic side effect of gentamicin in patients.