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Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance.

ABSTRACT: Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from human proximal tubular cell (HK-2) were used for in vitro evaluation of Vancomycin-induced alterations in cell viability, P-gp functionality, NAG, KIM-1 levels, and mRNA expression of NGAL and MMP-7. The in vivo efficacy of Renogrit against Vancomycin-induced nephrotoxicity was further evaluated in Sprague-Dawley (SD) rats by measurement of BUN, serum creatinine, and their respective clearances. Moreover, eGFR, kidney-to-body weight ratio, GSH/GSSG ratio, KIM-1, NAG levels and mRNA expression of KIM-1 and osteopontin were also analyzed. Changes in histopathology of kidney and hematological parameters were also observed. Renogrit treatment led to an increase in cell viability, normalization of P-gp functionality, decrease in levels of NAG, KIM-1, and reduction in mRNA expression of NGAL and MMP-7. In Vancomycin-challenged SD rats, Renogrit treatment normalized altered kidney functions, histological, and hematological parameters. Our findings revealed that Renogrit holds a clinico-therapeutic potential for alleviating Vancomycin-associated nephrotoxicity.

SUBMITTER: Balkrishna A

PROVIDER: S-EPMC10631690 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance.

Balkrishna Acharya A Sharma Sonam S Gohel Vivek V Kumari Ankita A Rawat Malini M Maity Madhulina M Sinha Sandeep S Dev Rishabh R Varshney Anurag A

PloS one 20231108 11

Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from hum ...[more]

PMID: 37939153

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Project description:BackgroundTraditional herbal medicine practitioners in the Ashanti region of Ghana use the fruit peels of Citrus limon (L.) Osbeck (C. limon) in preventive and curative treatment of many cancers including liver cancer. This ethnobotanical claim remains to be verified scientifically. Aim of the Study. This study investigated prophylactic hepatoprotective and anti-HCC effects of C. limon peel extract (LPE) in CCl4/olive oil-induced HCC-like rats.Materials and methodsAfter preparation of LPE, it was subjected to phytochemical screening using standard phytochemical methods. A total of 30 healthy adult male Sprague-Dawley rats (weighing 150-200 g) were randomly assigned into six groups of 5 rats each. Rats in the control group received olive oil (5 mL/kg ip) twice weekly for 16 weeks. Rats in the model group received CCl4/olive oil (2 mL/kg, ip) twice weekly for 16 weeks. Rats in capecitabine (10 mg/kg po) and LPE (50, 100, and 200 mg/kg po) groups received CCl4/olive oil (2 mL/kg, i.p) in the morning and their respective treatments in the afternoon twice a week for 16 weeks. Rats in all groups had free access to food and water ad libitum. Body weight and survival rates were monitored. Rats were sacrificed under deep anesthesia, blood was collected, and liver and other organs were isolated. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), prothrombin time, bilirubin, C-reactive protein (CRP), alpha- (α-) fetoprotein (AFP), and liver histology were assessed.ResultsAlkaloids, tannins, flavonoids, terpenoids, and saponins were detected in LPE. Model rats demonstrated increased serum levels of AFP, CRP, ALP, GGT, ALT, and AST, prothrombin time, total bilirubin, direct bilirubin, blood lymphocyte, and monocyte counts, but decreased serum albumin and total protein compared to control rats. Unlike the control, model rats demonstrated fat accumulation in periportal and centrilobular hepatocytes and neoplastic transformation. Semiquantitation of periodic acid Schiff- (PAS-) stained liver sections showed decreased glycogen storage in hepatocytes of model rats compared to control rats. Compared to the model, LPE treatment protected against CCl4-induced hepatocarcinogenesis, which was evidenced by decreased AFP, CRP, liver enzymes, total and direct bilirubin, prothrombin time, and blood lymphocyte and monocyte counts; attenuation of fat accumulation; and increased glycogen storage, albumin, and total protein.ConclusionLPE abates CCl4-induced hepatocarcinogenesis by attenuating liver inflammation and improving metabolic, biosynthetic, and detoxification functions of the liver. The prophylactic hepatoprotective and anti-hepatocarcinogenic effects of LPE are attributable to its phytochemical composition raising hopes of finding potential anticancer bioactive compounds from C. limon fruit peels.

Project description:IntroductionVancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed.MethodsTo address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group.ResultsPatients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity.ConclusionVancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.

Dataset Information

Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance.

Publications

Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance.

Similar Datasets

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