Gentamicin-induced Renal Damage Research Articles

Nephroprotective Effect of the Leaf Extract of Ajuga remota Benth Against Gentamicin-Induced Nephrotoxicity in Swiss Albino Mice.

Drug-induced kidney injury was among the most common renal damages, from which gentamicin occupies around 25% of this injury. Gentamicin-induced renal damage is caused by increased free radicals with subsequent amplified inflammation. Ajuga remota leaf extract has many phytochemicals with antioxidant activities, which may improve gentamicin-induced renal damage. Thus, we aimed to investigate the nephroprotective effect of Ajuga remota leaf methanolic extract on gentamicin-induced nephrotoxicity in Swiss Albino Mice. An experimental study design was used on 30 experimental mice randomly allocated in six groups: Group I, II, II, IV, and VI, among which mice were given only distilled water, only gentamicin, 600 mg/kg Ajuga remota leaf extract only, gentamicin along with 200 mg/kg extract, gentamicin with 400 mg/kg extract and gentamicin with 600 mg/kg extract, respectively. At the end of the experiment, the mice were sacrificed after being anaesthetized, and blood samples were collected through a cardiac puncture for renal function tests while the kidneys were removed for histopathological evaluation. The data were entered into Epidata version 4.6 and exported to SPSS version 25 for further analysis using one-way analysis of variance. Statistical significance was set at p < 0.05. Group II mice had significantly higher levels of serum creatinine and blood urea levels compared to group I and III. The body weight of the mice in group V and group VI showed a significant increase compared with Group II. Serum creatinine and blood urea levels were reduced significantly in the Ajuga remota leaf extract administered group of mice compared to group II. Abnormal kidney architectural changes were seen among group II mice; however, those changes were improved after administration of Ajuga remota leaf methanolic extract. Methanol extract of Ajuga remota leaf provided effective protection against gentamicin-induced oxidative renal damage through its antioxidant effects.

Investigation of antimicrobial and antioxidant activities of Chenopodium album extracts and their effects on gentamicin nephrotoxicity in rats.

This study aims to examine the antimicrobial and antioxidant activities of the aerial parts of Chenopodium album extracts (CAE) prepared with different solvents, and how C. album ethanol extract protects them against gentamicin-induced nephrotoxicity. Extracts of C. album aerial parts were obtained from ethanol, water, methanol, chloroform, and hexane solvents. Thirty-two male Wistar albino rats were used and gentamycin-induced nephrotoxicity was utilized as a model. The water extract of C. album exhibited no antimicrobial effect, whereas the methanol one created the highest zone diameter on Bacillus cereus (26 mm). The methanol extract displayed the highest activity in DPPH and ABTS. The ethanol extract yielded the highest reducing power in the CUPRAC. The water extract had the highest reducing power in the FRAP. Concerning gentamicin-induced renal damage, creatinine and urea levels in the blood were statistically higher in the gentamicin-C. album group compared to the other groups (p < .05). Urea and creatinine levels of the gentamicin-C. album group dropped significantly, indicating that the C. album was effective against renal damage. The sections from kidney tissues in the gentamicin + C. album group mostly exhibited mild glomerular congestion. Hyaline cast, cytoplasmic vacuolization, necrosis, and apoptosis were not observed. Thanks to C. album treatment, the gentamicin + C. album suffered less histopathological damage than the gentamicin group did. The results of the present study suggest that CAE can be used as a supportive treatment in people undergoing treatment for nephrotoxicity.

Comparison of the effect of vitamin C and selenium nanoparticles on gentamicin-induced renal impairment in male rats: a biochemical, molecular and histological study

Renal failure caused by gentamicin is mainly mediated through oxidative damage, inflammation, and apoptosis. Hence, vitamin C and selenium, which have antioxidant, anti-inflammatory, and anti-apoptotic properties, and their nanoparticle forms, which have recently received attention, may reduce gentamicin-induced side effects. Therefore, the aim of this study was to investigate the therapeutic effects of vitamin C and selenium, and their nanoparticles on gentamicin-induced renal damage in male rats. 128 adult male Wistar rats were randomly divided into equal sixteen controlled and treated groups. Serum levels of uric acid, blood urea nitrogen, urea, and creatinine were measured. Renal levels of oxidative parameters such as MDA, SOD, and CAT and inflammatory parameters including IL-1β, and TNF-α were measured. Renal expression of Nrf2, NF-κB, Bcl-2, caspase-3, BAX and mTORc1 was also evaluated. The results showed that gentamicin causes oxidative damage, inflammation, apoptosis and disruption of autophagy in kidney tissue in a dose-dependent manner. However, treatment with vitamin C, selenium and their nanoparticles could significantly improve these effects. Also, the results showed that the inflammatory and oxidative parameters and the expression of genes involved in them and apoptosis in the gentamicin groups treated with vitamin C nanoparticles and selenium nanoparticles reduced significantly compared to those treated with vitamin C and selenium. It can be concluded that vitamin C, selenium and their nanoparticles can improve gentamicin-induced kidney damage by inhibiting oxidative damage, inflammation and apoptosis-induced by autophagy, and can be a good option for kidney damage caused by gentamicin or as an adjunctive treatment to reduce its side effects.

Renal-Protective Activity of Dried Gel of Aloe barbadensis (Elwa) on Gentamicin- Induced Nephrotoxicity in Albino Rats

Introduction:: Elwa (Aloe barbadensis / Aloe vera) also known as Sibr in Unani medicine which is dried juice obtained by the inspissations and used to treat many diseases, especially digestive disorders, arthritis, gastric ulcer, jaundice, amenorrhoea, kidney diseases, diseases of spleen and liver, constipation, nervine disorders, wounds, burns, scalds and other skin diseases. Methods:: The aim of this study was to evaluate the nephroprotective activity of Aloe barbadensis gel (ABG) on gentamicin-induced nephrotoxicity in rats. Wistar rats were divided into four groups of six animals in each. Group I (control); group II, III and IV were administered gentamicin 100 mg/kg/d subcutaneously from day four to eight. The lower (350 mg/kg) and higher doses (1260 mg/kg) of crude ABG were co-administrated orally in group III and group IV from day 1. On 9th day animals were sacrificed and serum was studied for blood urea nitrogen and serum creatinine and kidneys were prepared for histo-pathological analysis. Gentamicin alone treated group showed increased levels of blood urea nitrogen (118.76  0.90) and creatinine (3.42  0.13) were significantly inhibited in groups pretreated with lower [blood urea nitrogen (40.130.56); creatinine (1.640.13)] and higher [blood urea nitrogen (55.79  0.71); creatinine (2.50  0.06)] doses of crude Aloe barbadensis gel. Results:: The histopathological analysis also showed the protective nature of Aloe barbadensis gel in gentamicin-induced renal damage. Discussion:: In conclusion, the biochemical parameters and histopathological results confirmed nephroprotective effect of the crude Aloe barbadensis gel against gentamicin induced renal damage.

Purslane (Portulaca oleracea) Ethanol Extract decreases hs-CRP levels and Total Score of Renal Tubular Degeneration in Rat Model of Gentamicine-Induced Renal Damage

Introduction: Injection of intraperitoneal gentamicin at a dose of 60 mg/kg BW intra-peritoneal in rats for 7 days has been shown to trigger renal tubular degeneration and increase in high sensitivity C-reactive protein (hs-CRP) level. The use of purslane (Portulaca oleracea) to reduce hs-CRP levels and total score of renal tubular degeneration has not been reported.Objective: to determine the effect of purslane ethanol extract on hs-CRP levels and renal tubular degeneration score in gentamicin induced-renal damage in rats.Methods: This was a study using posttest only control group design. Twentyfive male Wistar rats aged 8-12 weeks, weighed 150-200 grams were allocated into 5 groups: normal (Nor-G), without treatment; negative (Neg-G), gentamicin (60 mg/kg BW), intraperitoneally; P-200; P-300 ; P-400 (gentamicin plus purslane extract at a dose of 200, 300, and 400 respectively) for 7 days. The hs-CRP was evaluated using the ELISA method. Total score of renal tubular degeneration was evaluated using modified score of Sarjadi.Results: there was a significant difference in mean hsCRP level and total score of renal tubular degeneration between groups (p &lt;0.05). Posthoc analysis showed that hsCRP level and total score group of P-200, P-300 and P-400 were significantly lower than those of Neg-G, p &lt;0.05. Meanwhile, the levels of hsCRP and total score of renal tubular degeneration in P-200, P-300, P-400, and Nor-G groups were not significantly different (p&gt; 0.05).Conclusion: the administration of purslane ethanol extract at doses of 200, 300, and 400 mg/kg BW for 7 days improve hs-CRP level and total score of tubular degeneration similar to normal.

Ethanolic stem bark extract of Terminalia ivorensis A. Chev. protects against potassium dichromate–induced nephrotoxicity in rats

ObjectiveThe plant Terminalia ivorensis is used in traditional medicine as a diuretic and in the management of renal failure. We reported previously that the ethanol stem bark extract of the plant protects against gentamicin-induced renal and hepatic damage in rats. To further elucidate the mechanism of its renoprotective activity, we studied the effects of the extract on Potassium dichromate–induced nephrotoxicity in rats. The present study assessed the effectiveness of the ethanol stem bark extract of Terminalia ivorensis - against renal oxidative injury evoked by potassium dichromate. MethodsAdult Sprague Dawley rats pre-treated with (100–1000 mg/kg p.o. bwt) of Terminalia ivorensis extract for 5 days were challenged with a single dose of Potassium dichromate (20 mg/kg Sc) in the neck region on the 4th day. On the sixth day, renal function and markers of oxidative injury were assessed. ResultsTerminalia ivorensis (300–1000 mg/kg p.o) pre-treatment dose dependently prevented decreases in urine output in rats challenged with a nephrotoxic dose of Potassium Dichromate. The extract also protected the rats against Potassium dichromate-induced rise in serum electrolytes, urea and creatinine. Furthermore, it dose dependently prevented Potassium dichromate-induced decrease in renal glutathione (GSH) levels whereas tissue oxidative enzymes Superoxide dismutase (SOD) and catalase were protected from damage. Markers of lipid peroxidation such as level of renal Malondialdehyde (MDA) and myeloperoxidase (MPO) also decreased dose dependently when compare with Potassium dichromate treated groups. The extract also protected the histomorphology of the kidney against Potassium dichromate induced damage. ConclusionThe ethanol stem bark extract of Terminalia ivorensis protects kidney against Potassium dichromate-induced renal damage.

HPLC Analysis and In Vivo Renoprotective Evaluation of Hydroalcoholic Extract of Cucumis melo Seeds in Gentamicin-Induced Renal Damage.

Background and objectives: Cucumis melo, of family Cucurbitaceae, has traditionally been used to treat variety of kidney disorders. However to best of our knowledge there is no scientific study available that validates its renaoprotective uses. Therefore, this study aimed to evaluate nephroprotective effects of hydroalcoholic extract of Cucumis melo seeds (CMHE) and to identify its phytoconstituents. Materials and Methods: HPLC was performed to identify key phytochemicals of CMHE. Gentamicin (100 mg/kg/day, i.p) was administered to induce nephrotoxicity in Swiss albino mice for 8 days. Gentamicin (100 mg/kg/day, i.p) and oral CMHE were co-administered to mice at doses of 250 and 500 mg/kg to evaluate protective effects of CMHE. Normal control group mice were administered normal saline. Changes in body weights, biochemical and histopathological studies were conducted to establish nephroprotective effects of CMHE. Results: HPLC analysis indicated presence of quercetin, m-coumaric acid, gallic acid, chlorogenic acid, and trans-4-hydroxy-3-methoxy cinnamic acid in CMHE. Mice treated with CMHE showed significant increase in body weight and decrease in kidney weight as compared with toxic control group. Dose-dependent significant decrease in total blood urea nitrogen, serum creatinine, serum urea, and uric acid levels were observed in CMHE-treated groups as compared with toxic control group. Histopathological analysis of CMHE-treated groups showed improvement in kidney structures as compared with toxic control group. Conclusions: Biochemical, histopathological, and phytochemical screening of hydroalcoholic extract of Cucumis melo seeds suggest that it has nephroprotective potential. Furthermore, standardization of extract against identified phytochemicals, as well as long-term toxicological studies are suggested before commencement of clinical trials.

Nephroprotective properties of the methanol stem extract of Abrus precatorius on gentamicin‐induced renal damage through suppression of NF‐κB/CRP and enhancement of Bcl‐2 signaling pathways

The nephroprotective properties of methanol stem bark extract of Abrus precatorius against gentamicin‐induced renal damage in rats was evaluated in this study. Thirty (30) male Wistar rats were divided into five equal groups. Group A was the negative control group while B was the positive control group which received gentamicin 100 mg/kg intra‐peritoneally for six days. Group C were pretreated with 100 mg/kg extract for the three days and then concurrently with gentamicin 100 mg/kg for three days and group D were pretreated with 200 mg/kg extract for three days and then concurrently with gentamicin 100mg/kg for three days. Group E received gentamicin intraperitoneally for six days followed by administration of 200 mg/kg of the extract for 3 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analysis. The results showed that no significant haematological changes were noted. The groups treated with extract exhibited significant increase in body weight gain. While group B significantly exhibited focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy, the lesions were mild with the treated groups. Treated groups exhibited a dose dependent significant decrease in serum creatinine, urea, XO, NO and Myeloperoxidase, AOPP, Protein carbonyl, H2O2, MDA levels when compared with gentamicin treatment group. There were significant dose dependent improvements in SOD, GST, GSH, Protein thiol, and non‐protein thiol levels in the treated groups when compared with group B. In immunohistochemistry, gentamicin treatment group exhibited over expression of CRP and NF‐κB levels, and marked reduction in expression of Bcl‐2 while the reverse was seen in the groups treated with methanol extracts of Abrus precatorius.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Nephroprotective properties of the methanol stem extract of Abrus precatorius on gentamicin-induced renal damage in rats.

Background The use of plants for the treatment and prevention of diseases in man and his animals has led to a renewed scientific interest in the use of medicinal plants for therapeutic purposes. The nephroprotective properties of methanol stem bark extract of Abrus precatorius against gentamicin-induced renal damage in rats was evaluated in this study. Methods Thirty male Wistar rats were divided into five equal groups. Group A was the negative control group while B was the positive control group which received gentamicin 100 mg/kg intra-peritoneally for 6 days. Group C were pretreated with 100 mg/kg extract for the 3 days and then concurrently with gentamicin 100 mg/kg for 3 days and group D were pretreated with 200 mg/kg extract for 3 days and then concurrently with gentamicin 100 mg/kg for 3 days. Group E received gentamicin intraperitoneally for 6 days followed by administration of 200 mg/kg of the extract for 3 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analysis. Results The results showed that no significant haematological changes were noted. The groups treated with extract exhibited significant increase in body weight gain. While group B significantly exhibited focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy, the lesions were mild with the treated groups. Treated groups exhibited a dose dependent significant decrease in serum creatinine, urea, XO, NO and Myeloperoxidase, AOPP, Protein carbonyl, H2O2 generated and MDA levels when compared with group B. There were significant dose dependent improvements in SOD, GST, GSH, Protein thiol, and non-protein thiol levels in the treated groups when compared with group B. In immunohistochemistry, Group B exhibited over expression of CRP and NF-κB levels, and marked reduction in expression of Bcl-2 while the reverse was seen in the groups treated with methanol extracts of Abrus precatorius. Conclusion The methanol extract of Abrus precatorius plays a vital role against gentamicin induced renal damage by reducing levels of renal markers of oxidative stress, inflammation and apoptosis, enhancing enzymatic and non enzymatic renal antioxidant system, alongside an increase in Bcl-2 and a decrease in NF-κB and CRP expressions.

Nephroprotective Effect of Aqueous Extract of Pimpinella anisum in Gentamicin Induced Nephrotoxicity in Wistar Rats

Background: Pimpinella anisum known for its various medicinal properties is also a natural antioxidant and a free radical scavenger with no documented evidence as a nephroprotective agent. Objective: To evaluate the nephroprotective activity of aqueous extract of Pimpinella anisum seeds in a rodent model of gentamicin induced nephrotoxicity. Materials and Methods: Wistar albino rats of either sex, weighing 150–200 g was divided into 5 groups; normal saline, gentamicin 80mg/kg, intraperitoneally for 8 days, aqueous extract of Pimpinella anisum seeds at 1, 2, and 4g/kg, per oral for 8 days, the test extract administered 3 days prior and concurrently with gentamicin for 5 days. Blood urea, serum creatinine, uric acid and blood urea nitrogen analyses and microscopic examination of kidney were performed. Results: Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum urea, serum uric acid, serum creatinine and blood urea nitrogen (107.5±16.92mg/dl, 0.8±0.09 mg/dl, 3.05±0.29 mg/dl, 47.8±9.07 mg/dl) respectively when compared to the saline treated groups. Co-administration of Pimpinella anisum extract with gentamicin decreased the rise in these parameters in a dose dependent manner. Histopathological analysis revealed epithelial loss with intense granular degeneration in gentamicin treated rats, whereas aqueous extract of Pimpinella anisum mitigated the severity of gentamicin-induced renal damage. Conclusion: To conclude, our data suggest that aqueous extract of Pimpinella anisum exhibits renoprotective effect in gentamicin induced renal damage and further studies on its mechanism of action are warranted.

Ameliorative Properties of the Chloroform Stem Bark Extract of Abrus precatorius against Gentamicin-induced Renal Damage in Rats

Ameliorative Properties of the Chloroform Stem Bark Extract of Abrus precatorius against Gentamicin-induced Renal Damage in Rats

6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections.

Terminalia ivorensis A. Chev. Ethanolic Stem Bark Extract Protects Against Gentamicin-Induced Renal and Hepatic Damage in Rats

The aim of present study was to investigate the possible protective effects of an ethanolic stem bark extract of Terminalia ivorensis on gentamicin – induced nephrotoxicity and hepatotoxicity in male Sprague-Dawley rats. Groups of animals received either gentamicin alone or in combination with 100, 300 or 1000 mg/kg of extract for a period of 14 days. On the 15th day, the modulatory effect of Terminalia ivorensis was examined by assessing biochemical and renal markers of hepatic and renal damage. Markers of oxidative injury including reduced glutathione, superoxide dismutase, catalase and lipid peroxidation were assessed. Histology of the kidneys and the liver were also processed for analysis. The extract at a dose of 100-1000 mg/kg significantly reduced elevations in creatinine, urea and serum enzymes evoked by gentamicin. Additionally, the low levels of reduced glutathione and the antioxidant enzymes from the gentamicin treatment were significantly improved in the extract-treated animals. The results correlated well with the histopathological findings as the extract reversed the severe architectural distortions of the kidneys and liver caused by gentamicin. We conclude from the study that, the ethanolic stem bark extract of Terminalia ivorensis protects the liver and the kidneys against gentamicin-induced renal and hepatic damage.

Antioxidantal and histopathological effects of mirazid on gentamicin-induced renal damage in rats

The present study evaluates the biochemical effect of mirazid(MZ) in rats of GMtamicin(GM)- induced renal damage. Albino male rats (Rattus norvegicus), weighing 40–50 g were divided into 6 groups; normal saline, orally trated mirazid 10 mg/kg, GM 100mg/kg, intraperitoneally (i.p) for 10 days, MZ at 2.5, 5, and 10 mg/kg, per oral for 10 days with the same concentration of GM, MZ administered concurrently with GM for 10 days. We investigated the effects of MZ on GM-induced nephrotoxicity. GM treatment caused nephrotoxicity as evidenced by marked elevation in serum Cr and blood urea (152.3 ± 8.6 mg/dL, 1.6 ± 0.12 mg/dL resp) when compared to the saline treated group. GM administration increased renal MDA and NO GMeration but decreased SOD and CAT activities, and GSPx (glutathione peroxidase) compared to normal control. MZ administration with GM injections caused significantly decreased MDA, NO GMeration and increased SOD, CAT activities and GSPx activity when compared with GM alone. Histopathological analysis revealed epithelial loss with intense+granular deGMeration in GM treated rats, whereas MZ decrease the severity of GM-induced renal damage. To conclude, our data suggest that MZ exhibits some antioxidantal effect against GM nephrotoxicity, as it has a potent scavenger of free radicals to prevent the toxic effects of GM at both the biochemical and histological level and further studies on its mechanism of action and side effects are wanted.

Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies.Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats

Gentamicin is commonly used against gram-negative microorganisms. Its therapeutic use is mainly limited by nephrotoxicity. This study was aimed at evaluating the effect of rutin on oxidative stress, inflammation, apoptosis, and autophagy in gentamicin-induced nephrotoxicity in rats. The rats were treated with saline intraperitoneally (group I), 150 mg/kg of rutin orally (group II), 80 mg/kg of gentamicin intraperitoneally for 8 d (group III), or 150 mg/kg of rutin plus 80 mg/kg of gentamicin (group IV). The serum urea, creatinine, kidney malondialdehyde (MDA), and reduced glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and protein concentration were measured, and renal histopathology analysis and immunohistochemical staining were performed. Rutin pretreatment attenuated nephrotoxicity induced by gentamicin by reducing the urea, creatinine, and MDA levels and increasing the SOD, CAT, and GPx activity, and the GSH levels. The rutin also inhibited inducible nitric oxide synthase (iNOS), cleaved caspase-3 and light chain 3B (LC3B), as evidenced by immunohistochemical staining. The present study demonstrates that rutin exhibits antioxidant, anti-inflammatory, anti-apoptotic, and anti-autophagic effects and that it attenuates gentamicin-induced nephrotoxicity in rats.

Protective effects of metformin on renal tubular cells.

Dear Editor, Recently, we conducted a preclinical investigation to find the ameliorative properties of metformin on renal biochemical and histologic alterations of gentamicin-induced kidney damage in male Wistar rats (1). In this investigation, attenuation of gentamicin-induced acute kidney injury was found. Likewise, Taheri et al. conducted a study on the effects of metformin on renal tubular cells after unilateral ischemia reperfusion in rats’ kidney. They observed that metformin provided kidney protection against ischemia and reperfusion-induced injury (2). They concluded that metformin has tissue-protective effect through activation of adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (2). More recently we conducted a study on 70 male Wistar rats to test the efficacy of coadministrating garlic extract and metformin in prevention of gentamicin-induced renal tubular damage in Wistar rats (3). The result of this study showed that metformin, garlic juice, or their combination had both curative and protective effects on gentamicin-induced kidney injury. In addition, Kim et al. conducted a study using metformin for diabetic rats for 17 weeks and found that treatment of diabetic rats with metformin had restored podocyte loss. They suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by metformin through the repression of oxidative injury. They proposed that diabetes-induced podocyte loss in diabetic nephropathy could be reduced by metformin (4). Kim et al. found that the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) was decreased in the kidney of diabetic rats and metformin could restore its modification (4). Diabetic nephropathy is one of the most important complications of diabetes mellitus (5-11) and metformin has been broadly used for the treatment of type 2 diabetes (12). Thus, the suggestion of Baradaran et al. further attests our results and those by Taheri et al., which stated metformin protects against tubular injury by restoring the biochemical alterations and modulation of oxidative stress on the tubules (2, 3). Furthermore, according to the study of Kim et al. metformin protects podocytes in diabetic nephropathy (4). On the other hand, there is also tubular cell injury in diabetic nephropathy due to glycosuria (12-18). These findings can more potentiate the clinical use of metformin in the prevention of diabetic nephropathy. Previously, Morales et al. showed that gentamicin-induced renal tubular damage was attenuated by metformin (17). It is evident that metformin treatment significantly attenuates the increase in malondialdehyde and total reactive oxygen species generation and restores both enzymatic and nonenzymatic antioxidants to their physiologic levels (18, 19). These findings advocate the use of metformin in diabetes due to its protective effect on kidney beyond its blood regulatory effects. In fact, it is reasonable to illuminate three different actions of metformin including blood sugar regulatory property, renal tubular cell protection by acting as an effective antioxidant, and finally, protective effect on diabetic nephropathy through saving the podocytes (4, 18, 19). Hence, patients with diabetes might benefit from all of these three distinct protective properties (4, 18, 19). In this regard, more experimental or clinical studies are recommended to improve our knowledge regarding the kidney protective properties of metformin.

Flow cytometric evaluation of apoptosis on the effect of mirazid on gentamicin-induced renal damage in rats

The present study evaluates the effect of mirazid (mz) cd95 and cell cycle in rats of gentamicin (gm) induced renal damage for the detection of apoptosis. Albino male rats (rattus norvegicus), weighing 40–50 g were divided into 6 groups; normal saline, orally treated mirazid 10 mg/kg, gm i.p) for 10 days, mz at 2.5, 5, and 10 mg/kg, per oral for 10 days with the same concentration of gm, mz administered concurrently with gm for 10 days. Gm treatment caused nephrotoxicity as evidenced by marked elevation in serum creatinine and urea (152.3 ± 8.6 mg/dl, 1.6 ± 0.12 mg/dl resp) when compared to the saline treated group. Gm cause significant increase in both sub g1 (apoptosis) and cd95, marker of apoptosis, when compared to saline control whereas mz give significant decrease in cd95 (fas and fas ligand detection) and sub g1 (apoptosis).

The Ameliorative Effect of Zingiber officinale in Diabetic Nephropathy.

Dear Editor, Diabetic nephropathy is a progressive kidney disease and is characterized by diffuse glomerulosclerosis and nephrotic syndrome. Diabetic nephropathy is due to angiopathy of capillaries in the kidney glomeruli and is a prime indication for dialysis. It might be seen in patients with diabetes mellitus (DM) after about five years in type 1 diabetes and affects 25% to 35% of patients under the age of 30 years. Diabetic nephropathy is a progressive complication of DM that may lead to death two or three years after the initial injury. It is the end-stage kidney disease and the most common cause of chronic kidney failure. The risk of diabetes nephropathy is higher if blood glucose level and blood pressure are poorly controlled. Furthermore, people with high blood cholesterol level have much higher risk than those with normal cholesterol level (1-4). Nowadays attention has been drawn toward the possible kidney protective properties of Zingiber officinale (ginger) in these patients. To figure out the ameliorative effect of ginger extract against tubular damage induced by gentamicin, we conducted an experimental study in 60 male Wistar rats (6 groups of 10 rats). We treated them as follows: group I, vehicle; group II, ginger for three days and then gentamicin for seven days; group III, ginger orally for three days and then ginger plus gentamicin for seven days; group IV, gentamicin for seven days; group V, gentamicin for ten days; and group VI, gentamicin for seven days and then ginger orally for ten days. At the end of the study, kidneys were removed for histological evaluation. In this study, we observed that ginger could prevent degeneration of the renal cells and reduce the severity of tubular damage caused by gentamicin. We concluded that ginger was effective as a prophylactic agent for renal tubular cells against the acts of injurious substances like gentamicin (5). In the study conducted by Tzeng et al. the ameliorative effects of ginger on renal damage in diabetic rats was investigated. In their study, diabetic rats were treated orally with ginger or metformin for eight weeks. They found that ginger displayed similar characteristics to those of metformin in reducing hyperglycemia and renal dysfunction in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following the treatment with ginger. Furthermore, the protein expressions of renal nephrin and podocin in diabetic rats were significantly increased following the treatment with ginger. They suggested that the renoprotective effects of ginger might be similar to the action of metformin in the prevention of AMP-activated protein kinase protein phosphorylation (6). Metformin has been widely used in the patients with DM, especially in type 2 DM (7-10). Recently, the possible renoprotective role of metformin was noticed (7-10). In the study of Morales et al. ameliorative properties of metformin against gentamicin-induced renal tubular damage were shown (11). To find the potential efficacy of metformin in protecting kidney against gentamicin-induced acute kidney injury and to test whether delay treatment with metformin in acute kidney injury exerted similar efficacy on gentamicin-renal injury in rats, we conducted a study on Wistar rats. We found that metformin was able to prevent and ameliorate gentamicin-induced acute renal injury. Hence, it might have renoprotective efficacy (12). More recently, we observed the efficacy of coadministration of garlic extract and metformin in prevention of gentamicin–induced renal damage in 70 male Wistar rats (13-15). The result of these studies showed that metformin and ginger juice had ameliorative effects against gentamicin-induced nephrotoxicity. The protective effect of metformin on diabetic nephropathy was also recently published by Kari et al. (16). The incidence of DM and nephropathy of diabetes have risen rapidly (17-19). Therefore, the combination of metformin and ginger extract might be more effective to control of DM and might have additive protective efficacy on diabetic nephropathy. To better figure out the protective effect of ginger on kidney, particularly in combination with metformin, more researches are needed.

Nephroprotective and Curative Assessment of an Aqueous Seed Extract of Parkia clappertoniana Keay in Gentamicin-induced Renal Damage in Sprague-dawley Rats

Aim: To assess the nephroprotective and curative effects of an aqueous seed extract of Parkia clappertoniana on gentamicin-induced renal damage (GIRD) in Sprague-Dawley rats. Study Design: Experimental Place and Duration of Study: Department of Medical Laboratory, University of Cape Coast, Ghana between September, 2012 and May 2013. Methodology: In assessing nephro protective effect, rats were pretreated (10 days) with P. clappertoniana aqueous seed extract (1-2 g kg; p.o) prior to induction of renal damage by treatment with gentamicin (0.08g kg; p.o, for 8 days. Serum biochemical markers (Creatinine, Urea, Na and K) and urine parameters (leukocyte, protein, specific gravity and pH) of renal damage were determined and compared with baseline values. In a curative study, GIRD in rats was treated with Normal Saline (2 ml kg; p.o), Losartan Original Research Article European Journal of Medicinal Plants, 4(2): 234-248, 2014 235 (0.05 g kg; p.o), or extract (1-2 g kg; p.o) for 14 days and serum and urine parameters determined for all treatments. Histopathology and changes in kidney weights for normal and treated rats in both studies were assessed. The extract was screened for DPPH radical scavenging activity. Results: The extract significantly (P ≤ .001) reduced elevated serum creatinine and urea secondary to GIRD (P ≤ .05) and significantly (P ≤ .05) reduced elevated serum Na but had no effect on K. Elevated urine proteins and leucocytes secondary to GIRD was significantly (P ≤ .05) reduced; but had no significant effect on urine pH and specific gravity. Elevated kidney weights associated with GIRD was significantly (P≤ .01) reduced. Histopathological assessment revealed healing effect by extract to GIRD. Effects of the extract were similar to Losartan. Pretreatment with extract however had no significant effect on GIRD as serum and urine parameters, as well as kidney weights were significantly (P≤ .01) elevated on induction of renal damage. Conclusion: The aqueous seed extract of Parkia clappertoniana has curative but no nephroprotective effect on gentamicin-induced renal damage in Sprague-Dawley rats.