Gentamicin-induced Nephrotoxicity In Rats Research Articles

Nephroprotective Activity of Ethanolic Extract of Alternanthera sessilis Leaves in Gentamicin-induced Nephrotoxicity in Wistar Albino Rats

Background: Renal disease is a significant issue of global proportions and renal damage is very prevalent as the kidney has the ability to excrete toxic substances to assess the protective impact of the Ethanolic extract of Alternanthera sessilis Linn. (EEAS) plant leaves against gentamicin induced nephrotoxicity in rats. Materials and Methods: Nephroprotective activity was assessed by inflicting gentamicin (80 mg/kg) in all groups; acute kidney dysfunction is proven by the vital increment of blood serum creatinine, uric acid, BUN and decline in the total protein, albumin, and globulin with various histological damages. Results: Treatment with the Alternanthera sessilis has appeared critical dosage subordinate change at the measurements of 100 and 200mg/kg by securing the kidney from oxidative stretch. It is additionally recognized that treatment with Alternanthera sessilis essentially brought down the level of serum creatinine, uric acid, BUN and increment within the add up to protein, egg whites, globulin when compared to illness gather. Nephroprotective action of EEAS was found when compared with the standard bunch (Vitamin E 250 mg/kg) and control bunch against the infection gather creatures in parameters counting creatinine, urea, uric corrosive, Blood Urea Nitrogen (BUN), add up to protein, egg whites and globulin. The histopathological considers were moreover proving the defensive impact of EEAS. Conclusion: From the above results it was concluded that the ethanolic extract of Alternanthera sessilis offers nephroprotection.

Further insights into the impact of rebamipide on gentamicin-induced nephrotoxicity in rats: modulation of SIRT1 and β-catenin/cyclin D1 pathways

Gentamicin (GM) is an effective antibiotic administered to treat acute Gram-negative infections. Nevertheless, its clinical application is limited due to nephrotoxicity. Therefore, our research aimed to investigate the potential renoprotective impact of rebamipide (RBM), a gastroprotective drug, on GM-induced kidney damage in rats, as well as putative nephroprotective pathways. RBM was orally administered (100 mg/kg/d for 14 d) commencing 7 d before the administration of GM (100 mg/kg/d, intraperitoneally). Nephrotoxicity was elucidated, and the silent information regulator 1 (SIRT1) and β-catenin/cyclin D1 pathways were assessed. GM induced a significant elevation in the serum levels of creatinine, blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1), as well as the relative kidney index. In addition, GM increased lipid peroxidation and lowered total antioxidant capacity (TAC) level and superoxide dismutase (SOD) activity. GM administration also demonstrated a significant amplification in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor-κappa B p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), and caspase-3 kidney levels, as well as B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio. Notably, RBM treatment amended all these changes induced by GM. Furthermore, the potential role of SIRT1 and β-catenin-dependent signaling pathways in GM-induced renal injury was assessed. Our findings showed that GM-treated rats demonstrated a substantial decrease in SIRT1, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) along with an increase in β-catenin, forkhead box O-3a (FOXO-3a), and cyclin D1 protein expressions. RMB treatment markedly attenuated the deterioration caused by GM on these pathways. Additionally, RBM alleviated the GM-induced deleterious kidney tissue histopathology. In conclusion, our findings have verified that RBM can halt GM-induced renal injury by partly modulating SIRT1 and β-catenin pathways.

Chloroquine Attenuates Oxidative Stress in Gentamicin-Induced Nephrotoxicity in Rats.

The wider application of gentamicin is limited by potential adverse effects (nephrotoxicity and ototoxicity). The goal of our study was to investigate the effects of chloroquine on biochemical and oxidative stress parameters in gentamicin-induced nephrotoxicity in rats. Animals were randomly divided into 1 of 5 groups. First was Sham group (0.9% NaCl) (n = 8); second group received gentamicin (n = 8); while third (n = 8), fourth (n = 8) and fifth group (n = 8) received gentamicin and chloroquine in a dose of 0.3, 1 and 3 mg/kg, respectively. The urea and creatinine levels were significantly lower in chloroquine treated groups in doses of 0.3 mg/kg and 1 mg/kg (P < 0.001). Total oxidant status and the oxidative stress index showed significantly lower values in all chloroquine treated groups (P < 0.001; P < 0.005). Malondialdehyde was lower in chloroquine treatment in doses of 0.3 mg/kg (P < 0.005) and 3 mg/kg (P < 0.05). Chloroquine treatment markedly reduced the level of superoxide dismutase in doses of 1 mg/kg (P < 0.01) and 3 mg/kg (P < 0.05). Our study showed that chloroquine attenuates gentamicin-induced nephrotoxicity in rats regarding biochemical and oxidative stress parameters.

Protective effect of Crocus sativus stamens extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney

Crocus sativus is a medicinal plant supposedly possessing various biological activities. Currently, it is evaluated only by the medicinal properties of its stigma and many parts of this plant are unused. This work contributes to the valorization of C.sativus stamens by exploring the property of methanolic extract to prevent gentamicin-induced nephrotoxicity in rats. Twenty Wistar rats (weight 250 ± 30g) were assigned into four equal groups (n = 5), and among the assigned groups, group 1 was given only distilled water (Control), group 2 received intraperitoneal (i.p.) injection of gentamicin (GEN) 80 mg/kg/d, group 3 received the combination of gentamicin (80 mg/kg/d, i.p.) and oral administration of a lower dose of C. sativus methanolic extract (250 mg/kg/d), while the group 4 received the combination of gentamicin (80 mg/kg/d, i.p.) and oral administration of a higher dose of C. sativus methanolic extract (500 mg/kg/d). The injection of gentamicin for the nephrotoxicity induction and post-treatment with methanolic extract was carried out once a day for 15 days. For nephrotoxicity evaluation, biochemical and histopathological analyses were performed. The estimation of serum and urinary creatinine, blood urea nitrogen, sodium levels was carried out with the help of Architect Ci 4100 Analyzer. Oxidative stress was assessed by the determination of renal malondialdehyde (MDA) and catalase (CAT) levels. The results of the study suggested that gentamicin injection induced a significant (p &lt; 0.01) elevation in serum renal biochemical parameters and oxidative stress indices. The methanolic extract of C. sativus significantly (p &lt; 0.05) reduced serum creatinine, urea, and sodium levels, with an improvement in the histopathological results of gentamicin-induced alterations. Furthermore, pretreatment with plant extracts improved hepatic antioxidant status, by the elevation of the CAT and reducing the lipid peroxidation level (MDA) in tissues. The present study suggests that the methanolic extract of C. sativus stamens has an interesting nephroprotective effect on the renal lesions induced by GEN in modulating renal parameters and oxidative stress on Wistar rats.

Protective Effects of Mirazid on Gentamicin-induced Nephrotoxicity in Rats through Antioxidant, Anti-inflammatory, JNK1/ iNOS, and Apoptotic Pathways; Novel Mechanistic Insights

Background: As the use of Gentamicin became more widespread, the drug's harmful effects, particularly nephrotoxicity, became increasingly well-known. Antibacterial and anti-inflammatory properties have long been associated with Mirazid. This study aimed to investigate the frameworks for the protection of Mirazid against nephrotoxicity triggered by Gentamicin. Methods: Male albino rats were divided into three groups; the normal group received only saline. Nephrotoxicity was induced by Gentamicin (100 mg/kg; i.p.) for 10 days in the second group. In the third group; Mirazid (10 mg/kg; p.o.) was administered for 10 days before receiving Gentamicin. This was done to investigate the kidney/body weight index, serum creatinine, urea, lactate dehydrogenase (LDH), malondialdehyde (MDA), and Glutathione (GSH) levels. Moreover, immunohistochemical staining was done to study Jun N- terminal kinase 1 (JNK1), inducible nitric oxide synthase (iNOS), and caspase3 expressions along with histopathological changes. Additionally, a molecular docking study was performed for the seventeen isolated and identified compounds from myrrh, which is an oleo-gum resin obtained from the Commiphora species of plants (Burseraceae) against JNK1. Results: The Gentamicin group showed an increase in kidney/body weight index, serum creatinine, urea, LDH, and MDA, while decreasing GSH levels. Furthermore, immunohistochemical staining revealed increased JNK1, iNOS, and caspase3 expressions along with histopathological changes. Mirazid showed a significant decrease in all of these parameters and restored oxidant/antioxidant hemostasis. In addition, it has significantly preserved the histopathological architecture of tissues. Concerning the docking study, the isolated compound (12) was found to be superior to the co-crystallized inhibitor (18) with a binding score of -7.19 kcal/mol compared to -6.95, respectively. Conclusion: Current data demonstrated that Mirazid represented a viable approach to suppress the nephrotoxicity produced by Gentamycin through inhibiting JNK1/ iNOS pathways, thus preserving kidney function. Mirazid prophylactic efficacy is assumed to be due to its antioxidant, anti-inflammatory, and anti-apoptotic qualities.

Comparison of the therapeutic role of garlic extract and verapamil against gentamicin-induced nephrotoxicity in rats

Comparison of the therapeutic role of garlic extract and verapamil against gentamicin-induced nephrotoxicity in rats

Renoprotective Effect of Fucoidan from Seaweed Sargassum angustifolium C. Agardh 1820 on Gentamicin-Induced Nephrotoxicity: From Marine Resources to Therapeutic Uses

Background: Nephrotoxicity is a major side effect of aminoglycoside antibiotics, caused by oxidative damage and inflammation. Fucoidan, a group of sulfated polysaccharides derived from different species of brown algae, are well recognized for their antioxidant and anti-inflammatory activities. Objectives: In the present study, we aimed to investigate, for the first time, the efficacy of fucoidan extracted from Sargassum angustifolium C. Agardh 1820 against gentamicin-induced nephrotoxicity in rats. Methods: Twenty-eight male Wistar rats were divided into 4 groups of control, gentamicin (100 mg/kg), and gentamicin plus 50- and 100-mg/kg/day fucoidan pretreatment. In the end, all rats were killed, and then urine, blood, and tissue samples were prepared. Kidney weight (KW), body weight (BW), and 24-hour urine volume, as well as serum creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity, were measured. Kidney samples were also evaluated for histopathological changes. Results: Gentamicin significantly increased KW, KW/BW ratio, 24-hour urine volume, serum Cr, MDA, and BUN levels; however, fucoidan pretreatment, especially at a dose of 50 mg/kg, significantly returned these variables near to the control group values. Gentamicin also decreased BW gain, Cr clearance, SOD activity, and the degree of renal tissue damage compared to the control group, while treatment with fucoidan significantly reversed these alterations. Conclusions: The results show that fucoidan from S. angustifolium C. Agardh 1820 ameliorates gentamicin-induced nephrotoxicity by alleviating oxidative stress and augmenting antioxidant enzymes activity in renal tissue, suggesting the potential use of this fucoidan in a clinical setting.

Protective effects of p-coumaric acid against gentamicin-induced nephrotoxicity in rats

The most important side effect of gentamicin (GM) is nephrotoxicity. p-Coumaric acid (PCA) is a phenolic compound that scavenges free radicals, reduces fibrosis, and tissue damage. This study investigates the protective effect of PCA on tissue damage and kidney function in gentamicin-induced nephrotoxicity (GIN). Thirty-five rats were separated into five groups and each group contained seven animals: control group, ethanol group, GM group, PCA group, and GM + PCA group. At the end of the seven-day treatment, the rats were sacrificed after blood and kidney tissue samples were taken. While serum urea, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) levels increased significantly in the GM group compared to the control, they showed a significant decrease in the GM + PCA group compared to the GM. Serum tumor necrosis factor-α (TNF-α) and tissue malondialdehyde (MDA) levels were significantly increased in the GM group compared to the control. While the tissue total oxidant status (TOS) and oxidative stress index (OSI) values of the GM group were significantly higher than the control, they showed a significant decrease in the GM + PCA group compared to the GM. In the histopathological examination, significant tubular necrosis and tubulointerstitial inflammation were detected in the proximal tubules in the GM group compared to the control, while a significant decrease was observed in the severity of these findings in the GM + PCA group compared to the GM. This study shows that PCA has biochemical and histopathological ameliorating effects on GIN in the rat model.

Protective Effect of Opuntia dillenii (Ker Gawl.) Haw. Seed Oil on Gentamicin-Induced Nephrotoxicity: A Biochemical and Histological Analysis.

Opuntia dillenii is a medicinal plant with frequent usage in folk medicine to treat many illnesses. The present study aims to investigate the protective effect of Opuntia dillenii seed oil against gentamicin-induced nephrotoxicity in rats. The animals (rats) were randomly divided into three groups (i) the normal control group treated only with distilled water (10 mL/kg), (ii) the gentamicin group treated with distilled water (10 mL/kg) and received an intraperitoneal injection of gentamicin (80 mg/kg), and (iii) the group treated with the Opuntia dillenii seed oil (2 mL/kg) and also received an intraperitoneal injection of gentamicin (80 mg/kg). The rats received their following treatments for 14 consecutive days orally. Serum urea, creatinine, gamma-glutamyl transferase, albumin, and electrolyte levels were quantified as the markers of acute renal and liver failure. Besides, the kidney and liver relative weight, kidney malondialdehydes, and kidney histological analysis were determined. The results have shown that daily pretreatment with Opuntia dillenii seed oil (2 mL/kg) prevented severe alterations of biochemical parameters and disruptions of kidney tissue structures. In addition, the results of the present study showed for the first time that Opuntia dillenii seed oil reduced renal toxicity in gentamicin-induced nephrotoxicity in rats. Therefore, Opuntia dillenii seed oil may represent a new therapeutic avenue to preserve and protect renal function in gentamicin-treated patients.

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.

Aqueous Extract from Cinnamomum zeylanicum (Lauraceae) Stem Bark Ameliorates Gentamicin-Induced Nephrotoxicity in Rats by Modulating Oxidative Stress and Inflammatory Markers.

Nephropathies and especially nephrotoxicity have become one of the serious causes of life-threatening conditions because of intensive exposure to xenobiotic whether by environmental pollution or by drug abuse. The present study was undertaken to assess the protective effects of Cinnamomum zeylanicum stem bark aqueous extract (AECZ) on gentamicin-induced nephrotoxicity. AECZ was prepared by maceration in water and tested orally at the doses of 200 and 400 mg/kg/day to prevent gentamicin-induced nephropathies in male Wistar rats. Gentamicin (100 mg/kg/day) was administered for 14 consecutive days by intraperitoneal route, concomitantly with AECZ or silymarin (50 mg/kg/day) used as reference drug. Animal body weight was monitored during the treatment. After the last treatment on the 14th day, animals were sacrificed. Blood was collected for the evaluation of hematological and renal function biomarkers. The homogenate of one kidney was used to assess oxidative stress markers and proinflammatory cytokines, while the other one was fixed in formaldehyde for histopathological studies. Gentamicin decreased body weight, serum total proteins, and calcium level but increased kidneys' relative weight, serum creatinine, urea, and uric acid. Moreover, the levels of reduced glutathione, catalase, and superoxide dismutase activities were decreased, while an increase in malondialdehyde, proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and nitrites was observed in the negative control group as compared to normal control. Histological analysis of the kidney revealed the presence of tubular necrosis, glomerular degeneration, and macrophage infiltration in the gentamicin-treated group. All these impairment parameters were prevented by AECZ and silymarin treatments. AECZ has a protective effect against gentamicin-induced nephrotoxicity. The antioxidant and anti-inflammatory potentials of this extract may highly contribute to its nephroprotective activity.

Anredera cordifolia (Ten.) Steenis and Sonchus arvensis L. Inhibit Gentamicin-induced Nephrotoxicity

Introduction: Anredera cordifolia (Ten.) v Steenis and Sonchus arvensis L. have been used traditionally to treat many diseases such as inflammation, hypercholesterolemia, and kidney stones. This study investigated the renoprotective effect of the best combination of A. cordifolia (Ten.) Steenis and S. arvensis L. against gentamicin-induced nephrotoxicity in rats reduced the urinary N-acetyl beta-D-glucosaminidase (NAGase) specific marker. Materials and Methods: This study used male Wistar rats, weighing 200–300 g. The experiment consisted of a negative control group, a positive control group, A. cordifolia 100 mg/kg (body weight) b.w. group (AE), S. arvensis 100 mg/kg b.w. group (SE), A. cordifolia 50 mg/kg b.w. + S. arvensis 50 mg/kg b.w. (AE50 + SE50), A. cordifolia 100 mg/kg b.w. + S. arvensis 100 mg/kg b.w. (AE100 + SE100), A. cordifolia 75 mg/kg b.w. + S. arvensis 25 mg/kg b.w. (AE75 + SE25), and A. cordifolia 25 mg/kg b.w. + S. arvensis 75 mg/kg b.w. (AE25 + SE75). All groups were given the extract according to the group for 14 days orally. On day 15, all groups except the negative control group induced renal failure by administering gentamicin 100 mg/kg b.w. for 8 days along with the extract. On day 22, the evaluation was carried out by measuring urea, creatinine, and NAGase. Results: All treatment groups showed significantly decreased levels of creatinine and urea in serum and urinary NAGase when compared with the positive control group (P &lt; 0.05). The AE75 + SE25 group showed the smallest elevated levels of creatinine (14, 36%) and urea (17.4%) in serum and urinary NAGase (29.4%) when compared with the positive control group (P &lt; 0.05). Conclusion: The combination of A. cordifolia 75 mg/kg b.w. and S. arvensis 25 mg/kg b.w. extract showed a better nephroprotective effect in decreasing the NAGase as the early biomarker in kidney failure.

The protective effect of Origanum majorana essential oil on gentamicin-induced nephrotoxicity in rats.

Gentamicin (GM) is an aminoglycoside antibiotic used in gram-negative bacterial infection. The use of gentamicin causes nephrotoxicity. Origanum majorana (OM) a plant, has powerful antioxidant and anti-inflammatory properties. The aim of this study is to determine the protective effects of OM on GM-induced nephrotoxicity in rats. Rats were divided into 6 groups (n=8): The Control group: was given olive oil, OM (0,32 ml/kg) group: was given by gavage OM (0,32 ml/kg) for 28 days, OM (0,64 ml/kg) group: was given by gavage OM (0,64 ml/kg) for 28 days, GM group: was given 100 mg/kg/day intraperitoneally GM from the 21st to the 28th day, OM (0,32 ml/kg) +GM group: was given by gavage OM (0,32 ml/kg) for 28 days and was given 100 mg/kg/day intraperitoneally GM from the 21st to the 28th day, OM (0,64 ml/kg)+GM group: was given by gavage OM (0,64 ml/kg) for 28 days and was given 100 mg/kg/day intraperitoneally GM from the 21st to the 28th day. Kidney tissues were evaluated histopathologically. The TUNEL method was used for evaluation of the apoptotic index. Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels in the kidney tissue were measured by ELISA assay. Histopathological damage, TUNEL positive cell count and MDA level increased in the GM group compared to the Control group. Moreover, SOD and CAT levels decreased in the GM group. There was a decrease TUNEL positive cell count in OM (0,32 ml/kg) +GM and OM (0,64ml/kg) +GM groups compared to GM group. As a result, OM can be used as a protective agent to reduce kidney damage by suppressing apoptotic pathways and by increasing antioxidant capacity.

HPLC-ESI/MS profiling, phytoconstituent isolation and evaluation of renal function, oxidative stress and inflammation in gentamicin-induced nephrotoxicity in rats of Ficus spragueana Mildbr. & Burret.

Ficus spragueana Mildbr. & Burret (family Moraceae) was reported to have various biological activities. However, its activity in treatment of renal injury has not been investigated yet. The current study aimed to evaluate the effects of F. spragueana leaf extract on nephrotoxicity caused by gentamicin. Gentamicin is an important broad-spectrum antibiotic; nevertheless, it exhibits serious nephrotoxic adverse effects. HPLC-ESI/MS spectrometric analysis of the extract revealed the presence of 37 phenolic compounds. Moreover, five compounds were isolated from the leaf extract, and identified on the basis of spectroscopic analysis. The isolated compounds were syringic acid (1), p-coumaric acid (2), 3',5' O-dicaffeoylquinic acid (3), luteolin-8-C-β-D glucopyranoside (orientin) (4) and 8-methoxy kaempferol-3-O-[α-L-rhamnopyranosyl (1→2) β-D-glucopyranoside] (5). The gentamicin-induced nephrotoxicity model was used to evaluate the protective effect of F. spragueana on renal toxicity biomarkers throughout the development of acute kidney injury. Administration of extract led to improvement in kidney function through inhibition of kidney injury molecule-1, creatinine, blood urea nitrogen and total bilirubin, as well as decreasing the inflammatory markers interlukin1-beta and myeloperoxidase. Furthermore, it reduced the oxidative stress by increasing reduced glutathione and total antioxidant capacity levels while decreasing malondialdehyde and nitric oxide content, and improved renal histopathological injuries.

Evening Primrose Oil/ Vitamin E Combination Treatment Has Renoprotective Effect On Gentamicin-Induced Nephrotoxicity By Suppressing Renal Tumor Necrosis Factor α (TNF-α) / Nuclear Factor κβ (NF- κβ) Pathway And Inhibiting Renal Oxidative Stress

Gentamicin is an effective aminoglycoside antibiotic drug but unfortunately up to 30% of gentamicin-treated patients may develop nephrotoxicity. Suggested mechanisms of gentamicin-induced nephrotoxicity included inflammation and oxidative stress injury. Evening primrose oil (EPO) has anti-inflammatory and antioxidant effects. The aim of current study was to assess the possible renoprotective effect of EPO/vitamin E combination treatment on gentamicin-induced nephrotoxicity in rats. Additionally, to address the responsible mechanism(s) of this effect. Eighteen adult male albino Sprague-Dawley rats were equally and randomly divided into three groups; normal control, gentamicin control and EPO/vitamin E treated groups. Gentamicin control group and EPO/vitamin E treated group received IP gentamicin injections for 5 days (100 mg/kg). EPO/vitamin E treated group received EPO/vitamin E (10 g and 200 IU /kg/day respectively orally). Renal function, oxidative stress and histopathological changes were assessed. Renal tissue expressions of tumor necrosis factor α (TNF α) and nuclear Factor κβ (NF- κβ) were assayed. Significant improvements of kidney function markers and tubular necrosis in EPO/vitamin E treated group were observed. EPO/vitamin E treatment significantly ameliorated the gentamicin-induced increase of renal lipid peroxidation and renal tissue expression of TNF α and NF-κβ. EPO/vitamin E treatment significantly ameliorated the gentamicin-induced decrease of renal glutathione and superoxide dismutase concentrations. Conclusion of current study is EPO/vitamin E combination treatment has renoprotective effect on gentamicin-induced nephrotoxicity by inhibiting renal TNF α /NF-κβ signaling pathway and the oxidative stress. Further researches for addressing the renoprotective effect of EPO treatment only and to determine other possible responsible mechanisms are needed.

Xanthenone, ACE2 activator, counteracted gentamicin-induced nephrotoxicity in rats: Impact on oxidative stress and ACE2/Ang-(1–7) signaling

Nephrotoxicity is a rapid deterioration of kidney function due to exposure to nephrotoxic drugs as gentamicin. Gentamicin increases the generation of reactive oxygen species (ROS) leading to inflammatory responses and nuclear factor-κB (NF-κB) activation. The renal renin-angiotensin system (RAS) is considered a crucial regulator for physiological homeostasis and disease progression through the classic ACE/Ang-II/AT1 axis and its antagonist, ACE2/Ang-(1–7)/Mas axis which exerts an important role in the kidney. The present study evaluates the protective effects of the angiotensin-converting enzyme 2 (ACE2) activator; xanthenone; against experimental nephrotoxicity induced by gentamicin. Rats were divided into 4 groups, normal control, xanthenone (2 mg/kg, s.c), gentamicin (100 mg/kg, i.p. for one week) and xanthenone + gentamicin groups. Blood urea nitrogen (BUN) and serum creatinine levels were measured. The kidney tissues were used for estimating glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), NF-κB, Angiotensin II (AngII), and Ang-(1–7). In addition, histopathological examination and Western blot analysis of ACE2 expression were done. Xanthenone significantly restored serum levels of BUN and creatinine. Xanthenone exerted significant antioxidant effect as revealed by increased GSH content and SOD activity together with reduced MDA content. It exerted anti-inflammatory effect by significant reduction in TNF-α, NF-κB and IL-6 expression compared to gentamicin group. Xanthenone increased Ang-(1–7) and ACE2 expression while significantly decreased Ang-II expression. Histopathologically, xanthenone markedly counteracted gentamicin-induced renal aberrations. Activation of ACE2/Ang-(1–7) by xanthenone produced significant antioxidant and anti-inflammatory effects that counteracted gentamicin-induced nephrotoxicity.

Nephroprotective potential of Anogeissus latifolia Roxb. (Dhava) against gentamicin-induced nephrotoxicity in rats

Ethnopharmacological relevanceStem bark of Anogeissus latifolia Roxb. (Family: Combretaceae) is used traditionally and ethnomedicinally for correction of kidney disorders. Aim of the studyThe present study demonstrates the nephroprotective potential of stem bark of A. latifolia Roxb. Materials and methodsThe HPTLC fingerprint and HPLC analysis were carried out to standardize the ethanolic extract of stem bark of A. latifolia (ALEE) using ellagic acid as a marker. Nephrotoxicity was induced in adult Wistar albino rats by gentamicin (100 mg/kg, intraperitoneally for 8 days) and they were treated with ALEE (100, 200 and 400 mg/kg, orally for 8 days), ellagic acid (10 mg/kg, orally for 8 days) and cystone syrup (5 ml/kg, orally), a standard reference a polyherbal formulation. Urine volume, serum and urine levels of creatinine, urea and uric acid, oxidative stress parameters (lipid peroxidation, catalase, superoxide dismutase and reduced glutathione), inflammatory markers (TNF-α and IL-6) and kidney weight along with its histological changes were studied in experimental animals. ResultsHPTLC, HPLC and LC-MS analysis of ALEE revealed the presence of ellagic acid and other various phytoconstituents. Administration of gentamicin caused significant increase in urine output and kidney weight, elevated biochemical, inflammatory and oxidative stress parameters as well as caused histological damage in the kidney tissue. These parameters were attenuated by the concurrent treatment with ALEE and ellagic acid. The effects were comparable to cystone. ConclusionPresent investigations concluded that ALEE exhibited nephroprotective potential and validated the traditional use of stem bark of A. latifolia in kidney disorders. The nephroprotective effect may be attributed to the antioxidant and anti-inflammatory phytoconstituents in ALEE.

Anti-inflammatory, anti-oxidative and anti-apoptotic effects of Heracleum persicum L. extract on rats with gentamicin-induced nephrotoxicity

Objective: To evaluate the effect of Heracleum persicum L. against gentamicin-induced nephrotoxicity in rats. Methods: Thirty-six Wistar rats were divided into 6 groups including control (normal saline), gentamicin (80 mg/kg/d for 10 d), Heracleum persicum (750 mg/kg/d), and gentamicin (10 d) + Heracleum persicum extract at three different doses (250, 500, and 750 mg/kg/d for 40 d). Urine creatinine, urea, protein, and albumin levels were determined. In addition, serum urea, creatinine, sodium, potassium, cytokines (TNF-α, IL-1β, IL-6, and IL-10), glutathione peroxidase activity, total antioxidant capacity, kidney malondialdehyde, stereological parameters, and expressions of apoptosis-related genes (p53, Bax, Bcl-2, and caspase-3) were measured. The LD50 of Heracleum persicum extract was determined based on Lorke's method. Histopathological evaluation was also performed. Results: In addition to decreased urine protein and albumin, and increased creatinine and urea, co-treatment with gentamicin and Heracleum persicum significantly reduced levels of creatinine and urea, and increased sodium and potassium in serum. Heracleum persicum treatment also improved stereological parameters and serum inflammatory cytokines. There was a significant increase in serum glutathione peroxidase activity and total antioxidant capacity as well as a reduction in malondialdehyde level. Furthermore, treatment with Heracleum persicum extracts downregulated p53, caspase-3, and Bax and upregulated Bcl-2 expressions. In histopathological evaluation, Heracleum persicum extracts showed protection against gentamicin-induced renal damages. Conclusions: Heracleum persicum exhibits protective effects against gentamicin-induced structural and functional renal impairments.

Phytochemical analysis, antioxidant activity, and nephroprotective effect of the Raphanus sativus aqueous extract

&lt;p class="Default"&gt;In Morocco, Raphanus sativus is a widespread traditional medicinal plant used to treat various kidney diseases such as nephropathy.&lt;/p&gt;&lt;p class="Mabstract"&gt;&lt;strong&gt;Objective&lt;/strong&gt;:&lt;strong&gt; &lt;/strong&gt;The present study aims to evaluate the protective effect of the &lt;em&gt;R. sativus &lt;/em&gt;aqueous extract against the gentamicin-induced acute nephrotoxicity in rats.&lt;/p&gt;&lt;p class="Mabstract"&gt;&lt;strong&gt;Methods&lt;/strong&gt;: Rats were randomly separated into four groups (n=6; ♂/ ♀=1). The control group was treated only with distilled water (10 mL/kg; &lt;em&gt;p.o&lt;/em&gt;). The gentamicin group was treated with distilled water (10 mL/kg; &lt;em&gt;p.o&lt;/em&gt;) and injected intraperitoneally by the gentamicin (80 mg/kg; &lt;em&gt;i.p&lt;/em&gt;). &lt;em&gt;R. sativus &lt;/em&gt;groups were treated with the aqueous extracts of this plant at a dose of (200 or 400 mg/kg; &lt;em&gt;p.o&lt;/em&gt;) and injected by the gentamicin (80 mg/kg; &lt;em&gt;i.p&lt;/em&gt;). The plasma Creatinine, Urea, Uric Acid, Albumin, Total Protein, Alanine transaminase, Aspartate transaminase, and Calcium levels were measured. The urinary creatinine, urinary Calcium, urinary volume, water intake, creatinine clearance, body weight gain, relative right kidney weight, and kidney malondialdehydes were determined.&lt;/p&gt;&lt;p class="Mabstract"&gt;&lt;strong&gt;Results&lt;/strong&gt;: This study showed that the daily pretreatment with &lt;em&gt;R. sativus&lt;/em&gt; aqueous extract at two doses of 200 and 400 mg/kg, p.o prevented the rats from the gentamicin-induced nephrotoxicity. Moreover, the &lt;em&gt;R. sativus &lt;/em&gt;aqueous extract showed a high amount of polyphenols and flavonoids and a significant antioxidant activity.&lt;/p&gt;&lt;p class="Mabstract"&gt;&lt;strong&gt;Conclusion&lt;/strong&gt;: &lt;em&gt;R. sativus &lt;/em&gt;aqueous extract, as a novel natural product, may have preventive properties against gentamicin-induced nephrotoxicity in rats. The present study describes new areas of investigation to introduce better therapeutic agents for renal disorders and dysfunction.&lt;/p&gt;

Effect of camphor on biochemical factors and gene expression of antioxidant enzymes, inflammatory and apoptotic factors against gentamicin-induced nephrotoxicity in rats

Introduction: Camphor is a natural antioxidant with anti-inflammatory and tissue repair properties. Nephrotoxicity is the most important side effect of gentamicin (GEM) administration. Therefore, investigating the effect of natural antioxidants can resolve this complication. Objectives: We aimed to assay the effect of camphor on biochemical factors and gene expression of antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPX]) and inflammatory markers (tumor necrosis factor-alpha [TNF-α], nuclear factor kappa-B [NF-κB], interleukine-6 [IL-6]), and apoptotic indices (BCL2-associated X protein [Bax], B-cell lymphoma 2 [Bcl-2], caspase-3)], against GEM-induced nephrotoxicity in rats. Materials and Methods: Thirty adult male Wistar rats were allocated to five groups. Positive control and treatment groups were given GEM to induce nephrotoxicity. Animal treatment groups were treated with camphor in olive oil for 12 days. Renal biopsies, serum, extraction of renal tissue and urine of rats were taken after the twelfth day. Biopsies were examined for structural changes using a light microscope, moreover, apoptosis, desired biochemical and inflammatory factors, were investigated by suitable methods. Results: Camphor had no effect on biochemical factors, including malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), urea, creatinine and urine protein. However, it reduced the gene expression of TNF-α, NF-κB, IL-6, Bax, and caspase-3 and increased the gene expression of GPX and CAT and Bcl-2. Moreover, camphor improved kidney histopathological changes in the camphor groups in comparison with the GEM group. Conclusion: Camphor can be useful in the attenuation of GEM-induced nephrotoxicity based on expression levels of examined enzymes and factors and improving kidney histopathological changes.