Gentamicin-induced Nephrotoxicity Research Articles

Renoprotective effect of celecoxib against gentamicin-induced nephrotoxicity through suppressing NFκB and caspase-3 signaling pathways in rats

Gentamicin-induced nephrotoxicity has been well documented, although the causing mechanisms and preventative measures need further investigation. The current study aimed to explore the potential protective impacts of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on gentamicin-induced nephrotoxicity and the potential mechanisms in rats. Rats were randomly divided into four groups as follows: group1: normal control, group 2: received gentamicin only (100 mg/kg intraperitoneally), group 3: concurrently received gentamicin and celecoxib (30 mg/kg, orally) and group 4: received celecoxib.Celecoxib administration decreased gentamicin-induced rise in kidney weight, renal somatic index (RSI), blood urea nitrogen (BUN), serum creatinine (Cr), protein in urine, lactate dehydrogenase (LDH), nitric oxide (NOx), meanwhile, it increased serum albumin, urine Cr level and creatinine clearance (CCr), increased the renal endogenous antioxidant status, revealed by decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and reduced glutathione (GSH). Gentamicin-induced elevated nuclear factor kappa B-P65 subunit (NFκB-p65), tumor necrosis factor-alpha (TNF-α) and apoptotic markers (tumor suppressor protein (p53) and caspase-3) protein levels were significantly decreased upon celecoxib treatment. Moreover, celecoxib suppressed renal myeloperoxidase (MPO) activity and posed improvement of histological features. In immunohistochemistry, celecoxib-treated rats showed decreased immunoreactivity against COX-2 in tubular cells and a mild positive immunoreactivity against heat shock protein 70 (HSP70) in renal interstitial cells. These findings propose that celecoxib treatment mitigates renal dysfunction via decreasing renal inflammation, oxidative/nitrosative stress, and apoptosis.

Precise Monitoring of Drug-Induced Kidney Injury Using an Endoplasmic Reticulum-Targetable Ratiometric Time-Gated Luminescence Probe for Superoxide Anions.

Drug-induced acute kidney injury (AKI), caused by renal drug metabolism, has been considered to be a major barrier in drug development and clinical treatment. Among various drugs, anticancer drugs, cisplatin, and aminoglycoside antibiotic gentamicin, are known to be able to induce excessive or unfolded accumulation of proteins in the endoplasmic reticulum (ER) of cells, leading to ER stress. Meanwhile, reactive oxygen species (ROS) are formed, and superoxide anion (O2•-), the first produced ROS, is a key species to induce the AKI. Due to the lack of appropriate tools, the early diagnosis of AKI induced by cisplatin, gentamicin, or other drugs is still a crucial challenge. Herein, we report a lanthanide complex-based ER-targetable luminescence probe for O2•-, ER-(4'-trifluoromethanesulfonyloxy-2,2':6',2''-terpyridine-6,6''-diyl)bis(methylenenitrilo)tetrakis (aceticacid) (NFTTA)-Eu3+/Tb3+, for the sensitive monitoring of drug-induced AKI via mapping the generation of O2•- in live cells and laboratory animals. Using this probe coupled with the ratiometric time-gated luminescence (RTGL) imaging technique, the changes of O2•- level in the ER of live cells induced by different stimuli were precisely monitored. More importantly, the substantial increases in O2•- levels were observed in the cisplatin- and gentamicin-induced kidney injury of mice. In addition, the protective effects of l-carnitine (LC) and epigallocatechin-3-gallate (EGCG) against cisplatin- and gentamicin-induced nephrotoxicity were visualized and elucidated for the first time. The results demonstrated the potential of ER-NFTTA-Eu3+/Tb3+ for examining and monitoring O2•- in drug-induced AKI and for providing a diagnosis and treatment of nephrotoxicity diseases.

Sulphated polysaccharide from Sargassum myriocystum confers protection against gentamicin-induced nephrotoxicity in adult zebrafish

The beneficial effect of purified fraction of sulphated polysaccharide extracted from Sargassum myriocystum (SMP) was examined on the gentamicin-induced nephrotoxicity in adult zebrafish. The major purified fractions (SMP1, SMP2 and SMP3) were obtained by anion-exchange and size-exclusion chromatography and characterized by FTIR, GCMS and NMR. The in vitro antioxidant activities of all purified SMP fractions were analysed. The SMP2 showed maximum carbohydrate, sulphate and fucose content with strong antioxidant activity than other fractions. Further, we evaluated the efficacy of SMP2 against gentamicin-induced nephrotoxicity in zebrafish model. The SMP2 administered group showed a significant attenuation in oxidative stress and histopathological alterations observed in renal tissues of gentamicin treated group. Moreover, the SMP2 supressed renal mRNA expression levels of KIM-1, NF-κB, TNF-α and IL-6 in dose-dependent manner. Thus, the present study suggests that the SMP2 is a potent antioxidant with anti-inflammatory and renoprotective properties that ameliorated the GEN induced nephrotoxicity in adult zebrafish.

Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats

Gentamicin, belonging to the aminoglycosides, possesses the greatest nephrotoxic effect of all other antibiotics from this group. On the other hand, pioglitazone, which represents peroxisome proliferator-activated receptor γ (PPARγ) agonist recently showed antiinflamatory, antioxidative effects, amelioration of endothelial dysfunction etc. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. These effects were observed by following values of biochemical (serum urea and creatinine) parametars, total histological kidney score, urine level of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as well as parametars of oxidative stress (malondialdehyde, superoxide dismutase, catalase, total oxidant status, total antioxidant status, oxidative stress index and advanced oxidation protein products). It seems that pioglitazone protects the injured rat kidney in a U-shaped manner. Medium dose of pioglitazone (1 mg/kg, i.p.) was protective regarding biochemical (serum urea and creatinine), total histological score and the values of kidney injury molecule-1 (KIM-1) (P < 0.05 vs. control group, i.e. rats injected with gentamicin only). This finding could be of great importance for the wider use of aminoglycosides, with therapy that would reduce the occurrence of serious adverse effects, such as nephrotoxicity and acute renal failure.

Boron, a Trace Mineral, Alleviates Gentamicin-Induced Nephrotoxicity in Rats.

The present study was considered to assess the protective effects of boron (B) on gentamicin-induced oxidative stress, proinflammatory cytokines, and histopathological changes in rat kidneys. Rats were split into eight equal groups which were as follows: control (fed with low-boron diet); gentamicin group (100 mg/kg, i.p.); B5, B10, and B20 (5, 10, and 20 mg/kg B, i.p.) groups; gentamicin (100 mg/kg, i.p.) plus B5, B10, and B20 (5, 10, and 20 mg/kg B, i.p.) groups. B was given to rats 4 days before the gentamicin treatment and B administration was completed on the 14th day. Gentamicin administration was started on the 4th day and finished on the 12th day. Gentamicin increased malondialdehyde levels, while reduced glutathione levels in the blood and kidney. Furthermore, superoxide dismutase and catalase activities of erythrocyte were decreased. Besides, serum and kidney nitric oxide and 8-dihydroxyguanidine levels were increased by gentamicin. Additionally, serum levels and kidney mRNA expressions of TNF-α, NFκB, IL-1β, and IFN-γ were found to be the highest in the gentamicin group. Histopathologically, interstitial hemorrhage and tubular necrosis were detected in the kidneys of the gentamicin group. Nonetheless, B administration reversed gentamicin-induced lipid peroxidation, antioxidant status, and inflammation. In conclusion, B has a preventive effect against gentamicin-induced nephrotoxicity and ameliorates kidney tissues of the rat.

Nephroprotective Effect of Moringa Oleifera Seed Oil on Gentamicin-Induced Nephrotoxicity in Rats: Biochemical Evaluation of Antioxidant, Anti-inflammatory, and Antiapoptotic Pathways

Objective: Gentamicin is an efficacious aminoglycoside antibiotic widely used to treat life-threatening Gram-negative bacteria infections. However, its specific non-targeted induction of nephrotoxicity is a worrying clinical challenge. The study explored the nephroprotective effect of Moringa oleifera seed oil (MOO) against gentamicin-induced oxidative nephrotoxicity, pro-inflammation, and apoptosis in male Wistar rats. Method: Twenty-four rats divided into 4 groups (n = 6) were administered MOO (5 ml/kg) for 16 days and/or gentamicin (100 mg/kg bw/d, ip) injected from day 11 to day 16. The renal antioxidant enzyme activities reduced glutathione, lipid peroxidation, and serum renal markers. Urea and creatinine levels were estimated. The renal expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) were determined. Renal levels of inducible nitric oxide synthase (iNOS), nuclear factor-ĸB (NF-ĸB), and caspase-3 were determined to detect possible mechanism of inflammation and apoptosis with histology. Results: MOO prominently reduced serum creatinine and urea levels with amelioration of histopathological abrasions induced by gentamicin (GM). It significantly depressed oxidative stress through lowering of renal malondialdehyde (MDA) and elevation of renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) level. MOO restored renal content of IL-1β, IL-6, TNF-α, and NO, coupled with the mechanistic downregulation of NF-ĸB, iNOS, and caspase-3 activities. The histopathological alterations were ameliorated by MOO. Conclusions: MOO possesses marked nephroprotective effect against GM-induced renal damage via modulating oxidative stress, inflammation, and apoptosis in Wistar rats.

Renoprotective effect of irbesartan in a rat model of gentamicin-induced nephrotoxicity: Role of oxidative stress.

BACKGROUND:The renin–angiotensin system (RAS) is essential in renal physiology; however, disturbance of the RAS is one of the chief pathways involved in renal injury. Dysregulation of RAS may result in both glomerular and tubulointerstitial injuries through direct effects of angiotensin II (Ang II) type 1 receptor. Irbesartan and other Ang II blockers have renoprotective effect through reduction of on renal inflammations. Therefore, the aim of the present study was to demonstrate the renoprotective effect of irbesartan on gentamicin-induced nephrotoxicity in rats concerning the oxidative stress.MATERIALS AND METHODS:Thirty Sprague-Dawley Male rats 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 molecules (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.CONCLUSION:Irbesartan has renoprotective effect in attenuation of acute nephrotoxicity through modulation of oxidative stress and antioxidant capacity in rats.

Effect of calcium acetate and quercetin on gentamicin-induced nephrotoxicity in rat

Objective: The present work was conducted to evaluate the possible renoprotective effect of both calcium acetate and quercetin against gentamicin-induced nephrotoxicity in rat. Design: Controlled study. Animals: Seven groups of male albino rats. Procedures: Seventy, apparently healthy, male albino rats were haphazardlydivided into seven equal groups. Group 1: injected I.P with normal saline (control), Group 2: received gentamicin (80 mg/kg/d, I.P for 7 consecutive days), Group 3: received gentamicin plus lower dose of calcium acetate (75 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 4: received gentamicin plus higher dose of calcium acetate (200 mg/kg/d, orally for 7 consecutive days) simultaneously, Group 5: received gentamicin; afterwards, rats were treated with quercetin (50 mg/kg/d, orally for 7 consecutive days, Group 6: received quercetin; afterwards, rats were simultaneously treated with gentamicin plus quercetin with the same doses, and Group 7: received gentamicin, calcium acetate (lower dose), and quercetin simultaneously. Results: The study demonstrated the nephrotoxic impacts of gentamicin biochemically and histopathologically. Gentamicin treatment induced a significant increase in blood urea nitrogen (BUN) and serum creatinine levels besides a significant elevation in C-reactive protein (CRP) level. The significant increase in the tissue malondialdehyde(MDA) level and the significant reduction in the tissue superoxide dismutase(SOD) and glutathione(GSH) levels demonstrated that gentamicin-induced nephrotoxicity was mediated through oxidative stress reactions. Gentamicin-induced degenerative changes in renal tubules and glomeruli were also reported. Conclusion and clinical relevance: The use of both calcium acetate (lower and higher doses) or quercetin (therapeutically and prophylactically) in combination with gentamicin significantly minimized its nephrotoxicity as revealed from decreasing BUN, serum creatinine, CRP levels, oxidative stress reactions, and histopathological alterations with better protective effect of quercetin than Ca acetate. Co-administration of both calcium acetate and quercetin with gentamicin could prevent gentamicin-induced nephrotoxicity.

The protective effects of Ocimum basilicum extract against gentamicin-induced nephrotoxicity in male rats; an anti-inflammatory, anti-oxidative and antiapoptotic action

Introduction: Some studies are in favor of protective and anti-inflammatory effects of Ocimum basilicum (OB) against renal failure. Objectives: The aim of this study was to explore the protective effects of OB extract against gentamicin (GM)-induced nephrotoxicity in male rat models of acute kidney injury. Materials and Methods: Twenty-seven adult male Wistar rats with the weight of 200-250 g were prepared under standard condition (12 h light/dark cycle, 20 to 22°C temperature). In the gentamicin group (GM), the rats were administrated normal saline (5 mL/kg; oral) for four consecutive weeks and then GM (80 mg/kg/d; intraperitoneal) for another one week. In the third (OB-200+ GM) and fourth (OB-800+ GM) groups, the rats were initially treated with OB extract (200 mg/kg and 800 mg/kg respectively; oral) for four consecutive weeks followed by intraperitoneal administration of 80 mg/kg/d GM for another one week. The control group was treated with normal saline (5 mL/kg; oral) for five consecutive weeks. They were sacrificed under deep anesthesia, then plasma and tissue samples were obtained. Results: Treatment with OB hydro-alcoholic extract decreased BUN, serum Cr, FeNa and the levels of TNF-a and NF-kB and also diminished the rate of apoptosis in renal tubular cells compared to gentamicin group. Conclusion: Our findings provide comprehensive evidence supporting the beneficial role of OB, a traditional medicinal herb, as a potential therapeutic supplement to prevent the incidence and progression of renal impairment in GM-induced renal toxicity.

Improvement of renal profile in Gentamicin-induced Nephrotoxicity in albino wistar rats by edible macrofungi Dacryopinax spathularia and Schizophyllum commune

he present work has been taken to assess the pharmacological efficacy of two edible macrofungi Dacryopinax spathularia and Schizophyllum commune in the improvement of renal profile of Gentamicin-induced nephrotoxicity in albino wistar rats. The intra-peritoneal administration of gentamicin 80 mg/Kg Body Weight per day had resulted in alterations in renal function and renal damage which was reflected by abnormal and significant (p=0.05) increase in renal function parameters of blood like Urea, Creatinine, Uric Acid and Blood Urea Nitrogen (BUN). On administration of high dose (500 mg/Kg BW) of D. Spathularia extract to the nephrotoxic group of rats the concentration of urea, creatinine, uric acid and BUN significantly decreased from 104.26±7.45 to 76.27±7.24, 1.17±0.43 to 0.68±0.47, 3.68±1.34 to 2.58±0.56 and 48.72±4.36 to 31.14±3.76 respectively, in comparison to the nephrotoxic group of rats. On the other hand, the administration of high dose (500 mg/Kg BW) of S. commune extract to the nephrotoxic group of rats resulted into significant (p=0.05) decrease in the concentration of urea, creatinine, uric acid and BUN, from 104.26±7.45 to 51.42±6.15, 1.17±0.43 to 0.62±0.14, 3.68±1.34 to 2.36±0.74 and 48.72±4.36 to 28.65±3.85 respectively, in comparison to the nephrotoxic group of rats. The results also revealed that S. commune extract showed comparatively more efficacy in the renal profile improvement of nephrotoxic rats in comparison to the D. spathularia extract.

Effect Of Calcium Acetate And QuercetinOn Gentamicin‐Induced Nephrotoxicity In Rat

The present work was conducted to evaluate the possible renoprotective effect of both calcium acetate and quercetin against gentamicin-induced nephrotoxicity in rat. Seventy, apparently healthy, male albino rats were haphazardlydivided into seven equal groups. group 1: injected I.P with normal saline (control), group 2: received gentamicin (80 mg/kg/d, I.P for 7 consecutive days), group 3: received gentamicin plus lower dose of calcium acetate (75 mg/kg/d, orally for 7 consecutive days) simultaneously, group 4: received gentamicin plus higher dose of calcium acetate (200 mg/kg/d, orally for 7 consecutive days) simultaneously, group 5: received gentamicin; afterwards, rats were treated with quercetin (50 mg/kg/d, orally for 7 consecutive days, group 6: received quercetin; afterwards, rats were simultaneously treated with gentamicin plus quercetin with the same doses, and group 7: received gentamicin, calcium acetate (lower dose), and quercetin simultaneously. The study demonstrated the nephrotoxic impacts of gentamicin biochemically and histopathologically. Gentamicin treatment induced a significant increase in blood urea nitrogen (BUN) and serum creatinine levels besides a significant elevation in C-reactive protein (CRP) level. The significant increase in the tissue malondialdehyde(MDA) level and the significant reduction in the tissue superoxide dismutase(SOD) and glutathione(GSH) levels demonstrated that gentamicin-induced nephrotoxicity was mediated through oxidative stress reactions. Gentamicin-induced degenerative changes in renal tubules and glomeruli were also reported. The use of both calcium acetate (lower and higher doses) or quercetin (therapeutically and prophylactically) in combination with gentamicin significantly minimized its nephrotoxicity as revealed from decreasing BUN, serum creatinine, CRP levels, oxidative stress reactions, and histopathological alterations with better protective effect of quercetin than Ca acetate. Co-administration of both calcium acetate and quercetin with gentamicin could prevent gentamicin-induced nephrotoxicity.

"Nephroprotective Potential of Ethanolic Extract of Barks of Tricholepis Glaberrima Against Gentamicin Induced Nephrotoxicity"

"Nephroprotective Potential of Ethanolic Extract of Barks of Tricholepis Glaberrima Against Gentamicin Induced Nephrotoxicity"

Nephroprotective effect of Curcumin (Curcuma Longa) in acute nephrotoxicity in Sprague-Dawley rats

Objective: The objective of the present study was to evaluate the nephroprotective effect of curcumin in gentamicin induced-nephrotoxicity. Methods: Thirty Male Sprague-Dawley rats were used which divided into three groups, Group1 (n=10): Rats treated with distilled water plus normal saline for 12 days. Group2 (n=10): Rats treated with distilled water plus gentamicin for 12 days. Group 3(n=10): Rats treated with curcumin plus Gentamicin for 12 days. Blood urea, serum creatinine, malondialdehyde (MDA), kidney injury molecule (KIM-1) and cystatin-c were measured in both control and experimental groups. Results: Rats treated with gentamicin showed nephrotoxicity as evidence by significant elevation in serum creatinine, blood urea, KIM-1, MDA, Cystatin-C sera levels. Conclusion: Curcumin produced significant nephroprotective effect in gentamicin induced-nephrotoxicity through modulation of oxidative stress and inflammatory biomarkers.

Comparison of Effect of Silymarin and Ethanol Extract of Trigonella foenum-graecum on Gentamicin Induced Nephrotoxicity in Rats

Background: A variety of drugs and chemicals possess nephrotoxic potentials; therefore it is of keen interest to the researchers to obtain ways and means for alleviation of nephrotoxicity.&#x0D; Objective: The present study was designed to compare the ameliorative effect of silymarin with ethanol extract of Trigonella foenum-graecum in an experimental model of gentamicin- induced nephrotoxic rats.&#x0D; Methodology: This animal study was conducted by giving distilled water intraperitoneally to control group for seven days (1ml/rat/day) and was sacrificed on 8th day. To induce nephrotoxicity, gentamicin (GM) was administered (80 mg/kg/day for 7 days) intraperitoneally and sacrificed on 15th day. The ethanol extract of T. foenum-graecum was administered (500 mg/kg/day for 14 days) orally concomitantly with GM (7 days) and sacrificed on 15th day. To another group of rats, silymarin was administered (500 mg/kg/day for 14 days) orally concomitantly with gentamicin (7 days) and sacrificed on the 15th day. Biochemical indices like serum creatinine and serum urea levels were estimated to determine nephrotoxicity and amelioration of nephrotoxicity in all rat groups. To determine the status of oxidative stress and lipid peroxidation, the renal cortical glutathione (GSH) and renal cortical malondialdehyde (MDA) levels were estimated.&#x0D; Results: Statistically significant amelioration was observed in all the biochemical parameters in T. foenum-graecum and silymarin treated groups.&#x0D; Conclusion: The ameliorating effect of T. foenum-graecum is much more effective in comparison to that of silymarin in nephrotoxicity.&#x0D; Journal of Current and Advance Medical Research 2019;6(1):23-27

Kidney regeneration in Aphanius furcatus (Teleostei: Aphaniidae) after damage induced by gentamicin and evaluation of vitamin C in toxicity reduction

Gentamicin is known to stimulate the production of reactive oxygen species and lead to renal damage in some groups of vertebrates through oxidative stress. The kidney regeneration of the killifish Aphanius furcatus was studied after gentamicin-induced oxidative stress. In addition, we evaluated the possible role of vitamin C as an antioxidant in the reduction of renal toxicity. A total of 24 specimens (3.5-4cm in total length) were divided into four groups: In group-I two fish specimens treated with 7.5µl of normal saline injection; in group-II, 10 specimens received 10µg/g body weight (b.w) gentamicin; in group-III, two fish were treated with totally 60µg/g b.w vitamin C; and in group-IV, 10 specimens received both 10µg/g gentamicin and 60µg/g b.w vitamin C. The kidney tissues of group-I, III and IV were sampled during the nephrotoxicity phase (i.e., 10 hours post injection (hpi) to 5 days post injection (dpi)) and kidney tissues of group-II sampled daily for 10 dpi until regeneration completed. The kidney regeneration of A. furcatus through nephron neogenesis was detected by newly formed nephron on 8 dpi, and it is completed on 10 dpi. Our histological results in gentamicin-induced oxidative stress (group-II) clearly showed that the most severe damage is occurred in the kidney tissue within 1-4 dpi. However, in the specimens that antioxidant therapy supplied with vitamin C (group-IV), damage effect of gentamicin has remarkably repressed within these days. The outcome of this study revealed that administration of vitamin C is effective in reduction of gentamicin-induced nephrotoxicity in A. furcatus . Vitamin C reduces the toxicity effect of gentamicin by reduction of free radicals and reactive oxygen species (ROS) through its antioxidant activity. Therefore, using vitamin C together with gentamicin enhances the body resistance to the stress condition and reduces the toxicity effect of gentamicin.

Effect of Vitamin E on Serum Urea Level on Gentamicin Induced Nephrotoxicity in Long Evans Rats

Background: The kidneys have an important role in eliminating the final products of metabolic activities, excreting the drugs and chemicals. A variety of frequently used drugs have been demonstrated to produce nephrotoxic effects.&#x0D; Objective: This study was carried out to observe the effect of vitamin E on gentamicin-induced nephrotoxicity by assessing serum urea level in Long Evans rats.&#x0D; Materials and method: The experimental study was carried out on 40 healthy Long Evans rats of both sex with the weight ranges from 172-255 gm and the age ranges from 7 to 10 weeks. The rats were divided into four groups - Group A (normal control) received normal saline, group B, C and D received gentamicin for 6 days, rats of group C received vitamin E capsule for total 9 days with gentamicin whereas group D received vitamin E capsule for total 10 days with gentamicin. Serum urea level was measured at the end of the experiment.&#x0D; Results: The (mean±SD) serum urea levels in group A, B, C and D were 4.79±0.32, 12.41±1.22, 7.56±1.11 and 7.15±1.09 mmol/L respectively. The differences between groups were highly significant (p&lt;0.001) for group A &amp; B, A &amp; C, A &amp; D, B &amp; C, B &amp; D whereas the difference between C &amp; D (p&gt;0.01) was not significant. Serum urea level of the normal saline control group (group A) was within the normal limit (4.79 mmol/L). Serum urea level in gentamicin treated rats (group B) was more in comparison to gentamicin and vitamin E treated rats (group C &amp; D) and pretreatment with longer duration group (group D) showed lower serum urea value than shorter one (group C) though the groups showed no significant difference.&#x0D; Conclusion: Vitamin E treatment showed some protective effect against gentamicin-induced nephrotoxicity. The results also indicated that effectiveness of vitamin E depends on duration of pretreatment that means the pretreatment duration must be increased to a suitable period for better protection against gentamicin-induced nephrotoxicity.&#x0D; Delta Med Col J. Jan 2019 7(1): 11-15

Reno-protective effect of Rheum turkestanicum against gentamicin-induced nephrotoxicity.

Gentamicin belongs to the family of aminoglycoside antibiotics and is a preferred drug in developing countries because of its low cost, availability, and potent effects against bacterial. However, gentamicin can induce nephrotoxicity. In this research, hydroalcoholic extract of Rheum turkestanicum was used against gentamicin- induced nephrotoxicity and its effect against gentamicin-induced nephrotoxicity in rats has been investigated. The rats were placed into one of these groups: saline group, gentamicin group that received gentamicin 80 mg/kg/day for six days, and two treatment groups that received R. turkestanicum intraperitoneally at doses of 100 and 200 mg/kg body weight, respectively, 1 hr before gentamicin injections. Urine samples were collected at 24 hr to measure glucose and protein concentration. Blood samples were collected to determine serum urea and creatinine. One kidney was homogenized to measure malondialdehyde and thiol, and the other kidney was kept for pathological studies. Gentamicin increased the level of urinary glucose and protein, and increased malondialdehyde while it decreased thiol in kidney tissue, and increased the concentration of urea and creatinine in the serum. Histopathological pathology revealed renal damage following gentamicin usage; however, the extract was able to improve gentamicin toxicity. R. turkestanicum has positive effects in the attenuation of gentamicin-induced nephrotoxicity.

Pomegranate protects renal proximal tubules during gentamicin induced-nephrotoxicity in rats

Objective: The aim of present study was to evaluate the nephroprotective effect of pomegranate in gentamicin induced-nephrotoxicity in rats.&#x0D; Methods: Thirty Sprague Dawley Male rat were used, which randomly divided into 3 groups, 10 rats in each group. Group1 (n=10): Rats treated with distilled water for 12 days.Group2 (n=10): Rats treated with distilled water + Gentamicin .Group3 (n=10): Rats treated with pomegranate + gentamicin. Blood urea, serum creatinine, serum malondialdehde (MDA), superoxide dismutase (SOD) , glutathione reductase (GSH) , Neutrophil Gelatinase Associated Lipocalin (NGAL) , kidney injury molecules (KIM-1) and Cystatin-c were measured .&#x0D; Results: Blood urea and serum creatinine were significantly elevated in gentamicin group compared to the control p=0.007 and p=0.04 respectively. Also estimated GFR was significantly decreased in gentamicin group compared to the control p=0.04. Cystatin-c serum level and MDA serum level were increased but SOD and GSH were decreased insignificantly in gentamicin group compared to the control p&gt;0.05. Pomegranate reduced blood urea significantly p=0.002. Pomegranate improves endogenous anti-oxidant capacity since; it increase GSH significantly compared to gentamicin group p=0.02. There were insignificant effects on MDA and SOD. Moreover, pomegranate reduce serum levels of KIM-1and NGAL in gentamicin group p&lt;0.05.&#x0D; Conclusion: Pomegranate attenuates gentamicin induced-nephrotoxicity through potentiation of endogenous anti-oxidant capacity and inhibition of inflammatory pathway.

Effects of the Portulaca oleracea Extract on Gentamicin-Induced Nephrotoxicity in Male Rats

Background: Some data suggest the protective effect of Portulaca oleracea against renal failure and its association with the preservation of the renal antioxidant status and the regulation of apoptosis. Objectives: The current study aimed to examine the renoprotective effects of treatment with Portulaca oleracea (PO), a prominent hydrogen sulfide donor, in a 5/6 nephrectomy animal model. Methods: In this experimental study, 32 adult male Wistar rats, initially weighting 200 - 250 g, were housed under standard conditions since the beginning of April 2017 until the end of January 2018. The effect of PO extract on renal dysfunction induced by gentamicin was studied. The male rats were treated with two selected doses of PO (i.e., 200 and 600 mg/kg p.o.) and normal saline (5 mL/kg p.o.) for 28 consecutive days. Gentamicin (80 mg/kg/day intraperitoneally [i.p.]) was administered to two groups for seven days, and they were considered as the PO200 and PO600 gentamicin groups, respectively, while the group administered normal saline (5 mL/kg p.o.) for 35 consecutive days was considered as the control group. The rats were anesthetized on day 36. Then, they were sacrificed under deep anesthesia, and plasma and tissue samples were obtained. Results: Treatment with PO decreased the renal histological damages and apoptosis induced by gentamicin and enhanced renal function parameters compared to the gentamicin group. Conclusions: The present findings provide strong evidence to support the traditional medicinal use of this herb by the tribal people in the treatment of renal impairment. Finally, these results support the therapeutic effect of PO in preventing the development of renal dysfunction.

POMEGRANATE ATTENUATES ACUTE GENTAMICIN-INDUCED NEPHROTOXICITY IN SPRAGUE-DAWLEY RATS: THE POTENTIAL ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS

Objectives: Nephrotoxicity is a renal-specific situation in which the excretion of toxic metabolites is reduced due to toxic agents and drugs. Gentamicin is an antibiotic belongs to aminoglycoside group which may induce nephrotoxicity due to induction of oxidative stress. Pomegranate is a component of the traditional medicine called Punica granatum with significant nephron-protective effect. Therefore, the objective of the present study was to evaluate the nephronprotective effect of pomegranate in gentamicin-induced nephrotoxicity.&#x0D; Methods: A total of 30 male Sprague-Dawley rats were used which divided into Group 1 (n=10): Rats treated with distilled water 5 ml/kg plus normal saline 5 ml/kg for 12 days, Group 2 (n=10): Rats treated with distilled water 5 ml/kg plus gentamicin 100 mg/kg for 12 days, and Group 3 (n=10): Rats treated with pomegranate 100 mg/kg plus gentamicin 100 mg/kg for 12 days. Blood urea, serum creatinine, malondialdehyde (MDA), kidney injury molecule (KIM-1), and cystatin-C were measured in both control and experimental groups.&#x0D; Results: Rats treated with gentamicin showed nephrotoxicity as evident by significant elevation in serum creatinine, blood urea, serum creatinine, KIM-1, MDA, and cystatin-C sera levels. Pomegranate leads to significant reduction of blood urea and serum creatinine compared to gentamicin group, p&lt;0.05. Pomegranate also reduced MDA, KIM-1, and cystatin-C sera levels significantly compared to gentamicin group, p&lt;0.01.&#x0D; Conclusion: Pomegranate produced significant nephroprotective effect on gentamicin-induced nephrotoxicity through modulation of oxidative stress and inflammatory biomarkers.