Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats

Abstract

Background Cyclophosphamide (CP) is one of the potent and low cost chemotherapy used in clinical setting against a variety of tumors. However, its association with nephrotoxicity limits its therapeutic use. Ocimum gratissimum leaf is a medicinal plant with numerous pharmacological and therapeutic efficacies, such as antioxidant, anti-inflammation, and anti-apoptotic properties. Methods The present study was designed to evaluate the protective effect of Ocimum gratissimum (OG) against CP-induced kidney dysfunction in rats. Rats were pre-treated with 400 mg/kg b.w. of leave extract of Ocimum gratissimum (Ocimum G.) for 4 days and then 50 mg/kg b.w. of CP was co-administered from day 5 to day 7 along with Ocimum G. Markers of renal function and oxidative stress, food and water intake, electrolytes, aldosterone, leukocytes infiltration, inflammation and histopathological alteration were evaluated. Results Obvious renal inflammation and kidney injuries were observed in CP treated groups. However, administration of leave extract of Ocimum G. prevented oxidative stress, kidney injuries, attenuated inflammation, increased aldosterone production and reduced sodium ion and water loss in rats. The plasma creatinine, urea and urine albumin concentration were normalized after the administration of Ocimum G. extract in rats treated with CP. Ocimum G. also decreased the plasma concentrations of Interleukin-(IL)-6, C-reactive protein and activity of myeloperoxidase and malondialdehyde in CP treated rats. Conclusion Ocimum G. prevented kidney injury and enhanced renal function via inhibiting inflammation and oxidant-induced CP toxicity. The efficacy of Ocimum G. is related to the presence of various phytochemicals in the plant.

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Exhibits Antioxidant Mechanism for Abrogation of Cyclophosphamide-Induced Cardiac Damage and Oxidative Hepatorenal Toxicity in Rats

“…The induction of oxidative stress was confirmed by increased MDA level in this study. Our results are consistent with the published findings from systematic investigations showing CYP-induced depression of antioxidant apparatus and augmentation of lipid peroxidation in the liver, kidney and heart 4 15 23 . Interestingly, the STG protects the systemic antioxidant defences as indicated by the significant restoration of SOD, CAT, and GPx activities and level of GSH comparable to normal control.…”

“…More interestingly, the markers of renal and cardiac damage were also altered indicating CYP-induced cardiorenal injury in this study. However, studies have shown that CYP could damage the heart 23 , kidney 4 5 , testis 6 24 , and bladder 3 . In this study, CYP prominently increased levels of urea, creatinine as well as activities of cardiac CK and LDH ( Table 2 and Fig.…”

“…Urea and creatinine are the major serum indicators of renal injury 25 . Although CYP is commonly used due to its potency in killing cancer cells and survival rates, it retards renal capacity for ultrafiltration leading to increased levels of urea and creatinine in the blood 4 5 . Damage to myocardial cells activates increased activities of CK and LDH in the blood as observed in our study.…”

“…Unfortunately, the anticancer cytotoxic effect of CYP is not selective for cancer cells only; it affects healthy tissues and thus the prolong use of CYP has been associated with various organ toxicity [2]. The hepatic metabolites of CYP, acrolein and phosphoramide, are essentially known to incite bladder hemorrhagic cystitis and the antitumor efficacy, respectively [3,4]. Clinically, hepatotoxicity urotoxicity, nephrotoxicity, cardiotoxicity and gonadotoxicity remain significant constraints in CYP use [3][4][5][6][7].…”

“…The hepatic metabolites of CYP, acrolein and phosphoramide, are essentially known to incite bladder hemorrhagic cystitis and the antitumor efficacy, respectively [3,4]. Clinically, hepatotoxicity urotoxicity, nephrotoxicity, cardiotoxicity and gonadotoxicity remain significant constraints in CYP use [3][4][5][6][7]. Literature indicates that oxidative stress plays a chiefly role in CYP offtarget toxicities.…”