EXPERIMENTAL THERAPEUTIC EVALUATIONOF THE AFRICAN VEGETABLES(CLERODENDRUM VOLUBILE LEAF AND IRVINGIA GABONENSIS SEED EXTRACTS)IN TRASTUZUMAB-MEDIATED HEPATO-RENAL DYSFUNCTION IN EXPERIMENTAL RATS
Objective:The use of trastuzumab(TZM) in the clinical management of HER2 positive metastatic breast and gastric cancers, gastro-esophageal adenocarcinoma and colorectal carcinomahas been limited by its off-target cardiac, hepatic and renal toxicities which till date have no effective therapies in either their prevention or amelioration. Thus, the present study is designed atinvestigating the protective and therapeutic potentials of 400 mg/kg/day Clerodendrum volubile ethanol leaf extract (CVE) and Irivingia gabonensis ethanol seed extract (IGE) pretreatments in TZM-intoxicated Wistar rats based on their reported folkloric use in the local management of kidney and liver diseases and reported therapeutic potential in TZM cardiotoxicity.
Methods: Forty-nine male Wistar rats were randomly allotted into 7 groups of 7 rats per group. Group I rats were treated with 10 ml/kg/day of 5% DMSO sterile water p.o. and 1 ml/kg/day 5% DMSO sterile water i.p.; Groups II and III rats were orally pretreated with 400 mg/kg/day CVE and IGE, respectively, 3 hours before 1 ml/kg/day/i.p.5% DMSO sterile water; Group IV rats were orally pretreated with 10 ml/kg/day 5% DMSO sterile water 3 hours before 2.25 mg/kg/day/i.p.TZM; Groups V-VII rats were pretreated with 20 mg/kg/day Vit. C, 400 mg/kg/day CVE and 400 mg/kg/day IGE all dissolved in 5% DMSO sterile water, respectively, 3 hours before i.p. injections of 2.25 mg/kg/day TZM, all for 7 days. Liver function parameters, renal function parameters, oxidative stress markers and histopathological investigations were the study measuring endpoints.
Results: Oral pretreatment with 20 mg/kg/day Vit. C, 400 mg/kg/day CVE and IGE significantly ameliorated TZM-mediated hepatic and renal toxicities by effectively lowering the serum alanine transaminase, aspartate transaminase, alkaline phospahatase, creatinine and urea levels. CVEand IGE pretreatments also significantly reversed TZM-induced decreasesin the catalase, superoxide dismutase and glutathione-S-transferaseactivities and reduced malondialdehydelevels. CVE and IGE pretreatmentsalso improvedTZM-induced hepatic and renal histological lesions.
Conclusions:Overall, the chemotherapeutic/chemopreventive potentials of CVE and IGEin TZM-induced hepatorenal dysfunction wereeither wholly or partly mediated via free radical scavenging and antioxidant activities
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