Gentamicin In Rats Research Articles

Effect of Alogliptin and L-carnitine on Nephrotoxicity-Inducedby Gentamicin in Rats

Effect of Alogliptin and L-carnitine on Nephrotoxicity-Inducedby Gentamicin in Rats

Bufalin alleviates acute kidney injury by regulating NLRP3 inflammasome-mediated pyroptosis.

Recently, there has been an increasing clinical incidence of acute kidney injury (AKI), which rapidly declines renal function and leads to massive tubular cell necrosis. Pyroptosis is an inflammatory process of cell death that is more rapid than apoptosis, which is accompanied by a massive release of inflammasome activation. In the study, we aim to explore whether Bufalin regulates the AKI through the pyroptosis pathway. We have established gentamicin (GM)-induced AKI animal and cell models to simulate the pathological conditions of kidney injury. The expression of renal injury and pyroptosis-related indicators were detected by western blot. PAS staining and IHC staining were used to analyze renal function. CCK-8 assay was performed to detect cell viability after AKI with different treatments. TUNEL staining, flow cytometry and immunofluorescence assays were performed to measure pyroptosis. After intraperitoneal injection of GM in rats, renal function was significantly decreased, along with a significant increase of damaged and necrotic cells as suggested by renal tubular epithelial tissue sections. In addition, there was an increase in the pyroptosis-related markers expression and pyroptosis-induced cell death. Consistently, studies in vitro found that GM significantly induced pyroptosis and its associated protein expression in NRK52e cells. Whereas, the administration of Bufalin reversed these effects of GM in vivo and in vitro. Further, we found that Nigericin (NLRP3 agonist) could reversed the effects of bufalin on GM-induced pyroptosis. Bufalin attenuates pyroptosis generated AKI by inhibiting NLRP3 inflammasome.

Effect of Acacia nilotica Against Nephrotoxicity Induced by Gentamicin in Rat: Role of Antioxidants, Anti-Inflammatory and Antiapoptotic Markers

Effect of Acacia nilotica Against Nephrotoxicity Induced by Gentamicin in Rat: Role of Antioxidants, Anti-Inflammatory and Antiapoptotic Markers

Chemical Composition and Valorization of Broccoli Leaf By-Products (Brassica oleracea L. Variety: Italica) to Ameliorate Reno-Hepatic Toxicity Induced by Gentamicin in Rats

Broccoli (Brassica oleracea) is reported to possess antioxidant activity that could potentially prevent oxidative damage to tissues caused by many diseases. In the present study, we investigated the preventive effect of broccoli leaf by-product extract (BL) on gentamicin-induced renal and hepatic injury by measuring tissue antioxidant activities and morphological apoptotic changes. Broccoli leaf was thoroughly extracted with 70% methanol to yield the total methanol extract (TME). The total phenolic content (TPC) was determined. Thirty male rats were divided into five groups (six animals/group). Group I received phosphate-buffered saline orally, while group II was treated with gentamicin (100 mg/kg i.p. intraperitoneal) for ten days. Group III and group IV animals were given BL (200 mg/kg and 400 mg/kg, respectively) plus gentamicin treatment. Group V received L-cysteine (1 mmole/kg) plus gentamicin. Antioxidant and biochemical parameters, such as transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), creatinine, and urea, and mRNA expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and nuclear factor kappa B (NFkB) were determined in various groups, along with the quantification of inflammatory and apoptotic cells in hepatic and renal tissues. Malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels were determined in liver and renal samples. Histopathological studies of the liver and kidneys were also carried out. The TME was subjected to various and repeated techniques of chromatography to yield caffeic acid, gallic acid, and methyl gallate. The TPC was 6.47 mg Gallic Acid Equivalent/g of dry extract. Gentamicin increased the levels of serum AST, ALT, ALP, creatinine, and urea. The MDA and GSH contents and theactivity levels of the antioxidant enzyme SOD decreased in liver and kidney samples with gentamicin administration. BL administration dose-dependently prevented the alteration in biochemical parameters and was supported by low levels of tubular and glomerular injuries induced by gentamicin. This study valorizes the potential of BL as a preventive candidate in cases of gentamicin-induced liver and kidney toxicity and recommends further clinical studies using BL to validate its utilization for human consumption and as a source of phenolics for nutraceutical and pharmaceutical purposes.

Protective effect of Anodonta cygnea hemolymph against acute kidney injury induced by gentamicin in rats

Background: Anodonta cygnea hemolymph has several pharmacological activities against inflammation, bacteria and tumor. The current study aimed to explore the efficacy of A. cygnea hemolymph against the renal toxicity induced by Gentamicin (GM) in rats. Methods: The animals were divided randomly into three groups (six per group): control, GM and A. cygnea. Tissues toxicity established after injection of GM daily for eight days at dose 100 mg/kg. Kidney functions, liver functions, oxidative stress markers and histopathology of tissues investigated in the study. Results: A. cygnea treated rats showed a significant decrease in urea, creatinine, uric acid, ALT, AST, GGT and MDA levels while GSH and CAT levels increased. The histopathological of liver and kidney investigation showed partial restoration of renal architecture. Conclusion: This study showed the A. cygnea potency in improving the biochemical and histopathological changes in the kidney of the rats following experimental induction of toxicity using Gentamycin.

Intrarenal injection of silica mesoporous reduced renal toxicity induced by gentamycin in rats

Introduction: Mesoporous silica (MS) has recently used in biomedical applications due to its distinctive physicochemical properties. Purpose: The study aims to investigate the efficacy of MS to reduce renal toxicity induced by gentamicin in rats. Methods: The rats were randomly divided into three groups (n=6 per group): Control group (injected with 0.9% saline i.p daily for 8 consecutive), Gentamycin (injected with gentamycin, 100 mg/kg bw i.p. for 8 consecutive days) and MS group (after gentamycin injection, rat injected into left kidney with MS; 70 μg/0.5 ml/ rat). Results: Ms Treatment caused significant decreases in creatinine, urea, uric acid, and MDA while it increased GSH and catalase levels. Conclusion: Intrarenal injection of MS improved renal function in rats suffering from acute kidney injury.

Protective effect of Anodonta cygnea hemolymph against acute kidney injury induced by gentamicin in rats

Protective effect of Anodonta cygnea hemolymph against acute kidney injury induced by gentamicin in rats

Naja nubiae venom ameliorate hepatorenal toxicity induced by Gentamicin in rats

Naja nubiae venom ameliorate hepatorenal toxicity induced by Gentamicin in rats

Naja nubiae venom ameliorate hepatorenal toxicity induced by Gentamicin in rats

Background: In developing countries, there is no doubt that acute kidney injury and chronic liver diseases have a major impact on health. Different venom components are gaining renewed interest as potential sources of new pharmacological compounds relevant for human therapeutics. Aim: The present study was designed to evaluate the therapeutic efficacy of the crude venom extract of the Egyptian spitting cobra (Naja nubiae) venom extract against gentamycin–induced nephrotoxicity and hepatotoxicity in rats. Methods: Eighteen male Wistar rats were divided into three groups, control, gentamycin, and venom extract. The hepatorenal toxicity model was induced by gentamycin (80 mg/kg, intraperitoneal) for 8 days. Results: LD50 of venom extract in rats was 0.2mg/kg. The venom extract group showed a significant decrease in the liver enzymes, urea, uric acid, creatinine, malondialdehyde meanwhile glutathione reduced and catalase levels increased. Histological examination of liver and kidney mild protective efficacy with less extensive degenerative changes in the tissues of venom extract grou Conclusion: The results of the present investigation showed that administration of venom extract proved therapeutic efficacy against gentamycin -induced hepatorenal dysfunction by maintain the normal functional status of the liver and kidney and normalized the antioxidant system.

Sea cucumbers-saponin ameliorates hepatorenal toxicity induced by Gentamicin in rats

Sea cucumbers-saponin ameliorates hepatorenal toxicity induced by Gentamicin in rats

Sea cucumbers-saponin ameliorates hepatorenal toxicity induced by Gentamicin in rats

Background: Sea cucumbers have number of one of a pharmacological effects counting anticancer, anticoagulant, anti-inflammatory, antioxidant, and wound healing. Biological properties and therapeutic benefits of Sea cucumbers can be connected to the presence of a wide cluster of bioactive compounds particularly triterpene glycosides (saponins). Aims: The present study aimed to explore the hepatoprotective and nephroprotective activity of Sea cucumbers-saponin (Sc-S) on gentamicin-induced hepatorenal toxicity in rats. Main methods: Eighteen male Wistar rats were divided into three groups, control, gentamycin, and gentamycin+ Sc-S. The hepatorenal toxicity model was induced by gentamycin (80 mg/kg, i.p) for 8 days. Results: The Sc-S group showed a reduction in the concentrations of urea, uric acid, creatinine, MDA and the activities of AST, ALT, and ALP. While it caused a general increase in the levels of CAT and GSH. Microscopic examination appeared a clear enhancement in liver and kidney histology of Sc-S group. Conclusion: The antioxidant activity of Sc-S is the main mechanism for the protection of the liver and kidney against gentamicin toxicity.

Quercetin-loaded F127 nanomicelles: Antioxidant activity and protection against renal injury induced by gentamicin in rats

Quercetin (Q) is formulated into oil-in-water F127 microemulsions to improve its bioavailability. The size of the Q-loaded microemulsions system was about 8 nm by dynamic light scattering analysis. To compare antioxidant activity of bulk solution and microemulsion of Q, free radical scavenging activity was evaluated against 2,2-diphenyl-1-picrylhydrazyl (DPPH). The IC50 values were 56.77 and 187.68 μM, respectively. The drug in the bulk form released 16.34 times faster than microemulsion form. Although gentamicin (GM) has potent efficacy against gram-negative bacteria, it induces renal toxicity. Poor solubility and low bioavailability of Q as a bioflavonoid with potent antioxidant activity, limit its therapeutic application. We aimed to compare the effect of free Q and nanoencapsulated (NEQ) against GM-induced renal damage in Wistar rats. Forty-two animals were divided into six groups. Control and GM groups received apo-nanomicelles and GM (100 mg/kg) for 10 days. Two groups received Q (50 mg/kg, i.g.) and NEQ (50 mg/kg, i.g.) respectively for 10 days. Remaining two groups received Q and NEQ (50 mg/kg, i.g.) plus GM (100 mg/kg, i.p.) simultaneously for 10 days. After the experiments, serum and kidneys were used for biochemical, molecular and histological examinations. Immunohistochemical analysis was performed to explore kidney injury molecule-1 (KIM-1) expression as a specific protein biomarker of renal injury. Our findings indicated oxidative stress and altered histological features in renal tissue with deviated serum renal biomarkers in GM-treated rats. Although Q treatment in GM group tried to protect against GM-induced nephrotoxicity, but there were still differences compared to control rats. However, NEQ administration corrected elevations in the levels of urea, creatinine, uric acid and decrements in serum total proteins of GM group. Meanwhile, NEQ restored renal oxidative injury in GM rats through attenuation of lipid peroxidation and enhancement of antioxidant defense systems, glutathione, catalase and superoxide dismutase. NEQ could also normalize GM-induced abnormal renal histology features including fibrosis. Furthermore, the result of immunohistochemistry study confirmed these findings by undetecting KIM-1 expression in NEQ treated GM group, meanwhile showing this renal biomarker in GM and Q treated GM groups. Therefore, NEQ seems to be useful in protecting against renal oxidative stress and kidney damage in a rat model of GM nephrotoxicity which deserve further evaluations.

Protective Effects of Liposomal Curcumin on Oxidative Stress/Antioxidant Imbalance, Metalloproteinases 2 and -9, Histological Changes and Renal Function in Experimental Nephrotoxicity Induced by Gentamicin.

Background: Our study aimed to assess the efficiency of Curcumin nanoformulation (LCC) on experimental nephrotoxicity induced by Gentamicin in rats. Methods: Six groups of seven rats were used: C—(control group) received saline solution i.p. (i.p. = intraperitoneal), G—gentamicin (G, 80 mg/kg body weight (b.w.)), GCC1 and GCC2—with G and CC solution (single dose of 10 mg/kg b.w.-CC1, or 20 mg/kg b.w.-CC2), GLCC1 (10 mg/kg b.w.) and GLCC2 (20 mg/kg b.w.) with G and LCC administration. Oxidative stress parameters (NOx = nitric oxide, MDA = malondialdehyde, TOS = total oxidative stress), antioxidant parameters (CAT = catalase, TAC = total antioxidant capacity), matrix metalloproteinases (MMP-2 and MMP-9), and renal function parameters (creatinine, blood urea nitrogen, and urea) were measured. Kidneys histopathologic examination was made for each group. Results: Pretreatment with CC and LCC in both doses had significantly alleviating effects on assessed parameters (NOx, MDA, TOS, CAT, TAC, MMP-2, and -9) as compared with the untreated group (p < 0.006). Histopathological aspect and renal function were significantly improved in CC and LCC groups. Liposomal formulation (LCC) showed higher efficiency on all examined parameters compared to CC (p < 0.006). Conclusions: Our results demonstrated improving renal function and kidney cytoarchitecture, oxidative stress/antioxidant/balance, and MMPs plasma concentrations with better dose-related efficacity of LCC than CC.

Ocimum gratissimum (Linn) leaves extract attenuates oxidative stress and liver injury in gentamicin-induced hepatotoxicity in rats

ABSTRACT The adverse effect of gentamicin on tissues like kidney and liver makes its use limited in clinical settings. Ocimum gratissimum are known for many medicinal uses. The effect of aqueous extract (AOGL) and methanolic extract (MOGL) of Ocimum gratissimum (Linn) on liver following injury induced by gentamicin was investigated in this study. Forty adult (40) male Wistar rats were divided into 8 groups as follows: Group 1 (n = 5) received distilled water daily by oral route. Groups 2, 3, 4, 5, 6, 7 and 8 (n = 5) received 100 mg/kg/day of gentamicin i.p. for a week. After, groups 3, 4, 5, 6, 7 and 8 (n = 5) received 100, 200 and 400 mg/kg/day of AOGL and MOGL p.o, respectively, for 28 days. The rats treated with both AOGL and MOGL for 28 days were left for a recovery period of 14 days. Liver enzymes (ALT, AST and ALP), total bilirubin and total protein were determined in the plasma. TBARS and GSH levels were assayed in the liver homogenate. Gentamicin increases ALT, AST, ALP, total bilirubin and total protein, TBARS and decreases GSH, catalase and SOD of the toxic control when compared to the control group. Post-treatment with AOGL and MOGL in the treated groups caused increases GSH, catalase and SOD and decreases TBARS, ALT, AST, ALP, total bilirubin and total protein when compared with the toxic control group. The results show that AOGL and MOGL are capable of ameliorating liver injury caused by gentamicin in rats.

Protective Effect of Procambarus Clarkia Hemolymph against Acute Kidney Injury Induced by Gentamicin in Rats

Background: P.clarkii hemolymph has several pharmacological activities against inflammation, bacteria and tumor. The current study aimed to explore the efficacy of P.clarkii hemolymph against the renal toxicity induced by Gentamicin (GM) in rats. Methods: The animals were divided randomly into three groups (six per group): control, GM and P.clarkii. Tissues toxicity was established after injection of GM daily for eight days at a dose 100 mg/kg. Kidney functions, liver functions, oxidative stress markers and histopathology of tissues were investigated in the study. Results: P.clarkii treated rats showed a significant decrease in urea, creatinine, uric acid, ALT, AST, and MDA levels while GSH and CAT levels increased. The histology of kidney investigation showed partial restoration of renal architecture. Conclusion: The study results revealed the protective role of p.clarkii hemolymph against gentamicin-induced acute kidney injury in rats.

Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency.

Gentamicin is a used antibiotic that causes nephrotoxicity in 10–20% of treatment periods, which limits its use considerably. Our results have shown that cilastatin may be a promising therapeutic alternative in toxin-induced acute kidney injury (AKI). Here, we investigated its potential use as a nephroprotector against gentamicin-induced AKI in vitro and in vivo. Porcine renal cells and rats were treated with gentamicin and/or cilastatin. In vivo nephrotoxicity was analyzed by measuring biochemical markers and renal morphology. Different apoptotic, oxidative and inflammatory parameters were studied at cellular and systemic levels. Megalin, mainly responsible for the entry of gentamicin into the cells, was also analyzed. Results show that cilastatin protects cells from gentamicin-induced AKI. Cilastatin decreased creatinine, BUN, kidney injury molecule-1 (KIM-1) and severe morphological changes previously increased by gentamicin in rats. The interference of cilastatin with lipid rafts cycling leads to decreased expression of megalin, and therefore gentamicin uptake and myeloid bodies, resulting in a decrease of apoptotic, oxidative and inflammatory events. Moreover, cilastatin did not prevent bacterial death by gentamicin. Cilastatin reduced gentamicin-induced AKI by preventing key steps in the amplification of the damage, which is associated to the disruption of megalin-gentamicin endocytosis. Therefore, cilastatin might represent a novel therapeutic tool in the prevention and treatment of gentamicin-induced AKI in the clinical setting.

Ameliorative effect of cotreatment with the methanolicleafextract of Urtica dioica on acute kidney injury induced by gentamicin in rats.

Effects of cotreatment with Urtica dioica (UD) methanolic leafextract on gentamicin (GM)-induced acute kidney injury were evaluated in rats. Male Wistar rats (n=32) were separated into four groups. Gentamicin (100 mg/kg/day, IP) was injected for eight days with or without UD methanolic extract (200 mg/kg/day, gavage). The renal blood flow (RBF) and systolic blood pressure of rats were recorded. Concentration of creatinine, blood urea nitrogen (BUN), sodium, and potassium and osmolarity were measured in the urine and plasma samples. Oxidative stress level was determined by assessment of the levels of antioxidant power (FRAP) and lipid peroxidation (MDA) in the renal tissue. The renal injury and histopathological changes in the kidney were determined by microscopic evaluations. Administration of UD extract along with GM, compared to GM group, significantly decreased the amounts of plasma creatinine and BUN, urinary sodium excretion, fractional excretion of sodium and potassium, and MDA levels but significantly increased creatinine clearance, urine osmolarity, renal blood flow and FRAP levels. The cotreatment of UD extract can attenuate renal injury of GM by reduction of oxidative stress, lipid peroxidation, and oxygen free radicals. The potential nephroprotective effects of UD extract are probably mediated via its antioxidant and anti-inflammatory activity.

The Oral Post-Treatment Effect of Hydroethanolic Extract of Origanum Vulgare on Acute Kidney Injury Caused by Gentamicin in Rats

The Oral Post-Treatment Effect of Hydroethanolic Extract of Origanum Vulgare on Acute Kidney Injury Caused by Gentamicin in Rats

Nephroprotective activity of Sinapis alba in gentamicin induced murine model of renotoxicity

Sinapis alba, belongs to the family Brassicaceae and is known to possess an antioxidant capacity. Based on this background, this study was planned to look for the nephroprotective activity of Sinapis alba seed extract against nephrotoxicity caused by gentamicin in rats. Sinapis alba seeds were dried in the shade and then powdered. Then, the powder was subjected to extraction with 95% ethanol and brought to a syrup consistency by distilling the solvent and reducing the pressure using a water bath. Animals were divided into four groups. Each group had six animals in it. Group 1 serves as normal control, while the next group was disease control (received gentamicin). The rats in third and fourth groups were treated with the extract of Sinapis alba (200 and 400 mg/kg). The animals were sacrificed, and biochemical and histopathological studies were carried out after the 8th day of study. Results of the study showed positive effects with 200 mg/kg as well as 400 mg/kg doses of Sinapis alba extract. Serum urea, creatinine, and BUN was reduced significantly in the test group compared to the group which received gentamicin (p&lt;0.05). Moreover, this biochemical evidence was also validated with the histopathological results indicated with the absence of necrosis and casts in the tubular lumen. Ethanolic extract of Sinapis alba administered by the oral route in an experimental murine model using gentamicin as an instigator of damage to the kidney, effectively reduced renal damage in rats, therefore provides a scientific evidence of a renoprotective effect.

Protective effect of thymol and carvacrol on gentamycin-induced oxidative stress in male Albino rat

The current study aimed to investigate the protective effect of the thymol (20 mg/kg BW) or carvacrol (15mg/kg BW) on gentamycin (100mg/kg) induced oxidative stress in rat. Thymol and carvacrol were administrated orally once daily for 12 consecutive days. After one week of acclimatization, 30 adult male albino rats weighting 150-200g were used for the experiment. They were allocated into 5 equal groups (n=6). group1 (control), group2 (tween), group3 (gentamycin), group4 (thymol+gentamicin), and group5 (carvacrol+gentamcin). At the end of experiment, Rats were euthanized humanly and blood samples were collected to study the nephro, hepatic and inflammation markers. The findings revealed that there were significant decrease in serum blood urea nitrogen, creatinine and MDA in thymol and carvacrol groups but there were significant elevation in renal SOD, CAT and GPX. There were significant decreases in ALT, ALP, AST and GCT in thymol and carvacrol groups. Additionally, CRP, IL6 and TNF –α were decreased in thymol and carvacrol gps. The result revealed that each of the thymol and carvacrol has antioxidant and protective effects against the hepatic toxicity and nephrotoxicity induced by gentamicin in rats.