Abstract

Background and Purpose: Hepatorenal toxicity is a side effect of the anthracycline cytotoxic antibiotics, doxorubicin that is used in cancer treatment. The study investigated the ameliorative potential of Clerodendrum volubile ethanol leaf extract (CVE) on doxorubicin (DOX)-induced hepatorenal toxicities.
 Methods: Male Wistar rats were pretreated with Clerodendrum volubile ethanol leaf extract (50 - 400 mg/kg/day, p.o) followed by intraperitoneal injection of 2.5 mg/kg of DOX on alternate days for 14 days. Hepatorenal toxicity was assessed using renal function parameters (serum electrolytes, blood urea and creatinine), hepatic function endpoints [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total protein (TP), albumin (ALB) and total bilirubin (TB)]. In addition, the antioxidant activity in the kidney and liver tissues were assayed and histological studies of these tissues were also conducted.
 Results: Oral pretreatment with 50 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day and 400 mg/kg/day of CVE remarkably ameliorated DOX-induced liver and kidney injury by lowering the serum ALT, AST, ALP, Cr and BUN levels. CVE pretreatment remarkably ameliorated DOX-induced increases in the CAT, SOD and GPx activities and MDA levels compared to the DOX-treated rats. The biochemical changes were corroborated by improvements in the DOX-induced histological lesions seen in the hepatic and renal tissues examined.
 Conclusions: Overall, these findings suggest that Clerodendrum volubile ethanol leaf extract elicits protective effect against DOX-induced hepatorenal toxicities mediated primarily via oxidative stress suppression and improvement in the free radicals scavenging activities of CVE.

Highlights

  • Doxorubicin (DOX) is one of the widely used broad spectrum anthracycline antibiotics and one of the most potent cytotoxic drugs use in the clinical management of solid and hematological malignancies (Injac and Strukelj, 2008; Chen et al, 2016)

  • In continuation of our investigation into the possible therapeutic potentials of Clerodendrum volubile ethanol leaf extract (CVE) against doxorubicin-induced organ toxicities, this study investigated the possible potential of CVE against DOX-induced hepatorenal toxicities

  • Effect of CVE on Body Weight Changes of Doxorubicin-treated Rats Table 2 shows the effect of repeated intraperitoneal doxorubicin injections and oral pretreatments with 50, 100, 200 and 400 mg/kg/day of CVE on the average body weight on day 1 and day 14 as well as percentage weight change (%∆wt.) of rats

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Summary

Introduction

Doxorubicin (DOX) ( known as Adriamycin) is one of the widely used broad spectrum anthracycline antibiotics and one of the most potent cytotoxic drugs use in the clinical management of solid and hematological malignancies (Injac and Strukelj, 2008; Chen et al, 2016).These malignancies include but not limited to cancers of the breast, lungs, thyroid, urinary bladder and ovaries, Kaposi's sarcoma, Hodgkin‟s lymphoma and acute lymphocytic leukemia for which it is often combined with other cytotoxic agents (Tacar et al, 2013). DOX stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby halting replication (Pommier et al, 2010) It is often combined with other cytotoxic agents such as cyclophosphamide, bleomycin, vinblastine, vincristine, prednisolone, 5-fluoruracil, in cancer treatment “cocktails” (Rivankar, 2014). The study investigated the ameliorative potential of Clerodendrum volubile ethanol leaf extract (CVE) on doxorubicin (DOX)-induced hepatorenal toxicities.

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