TY - JOUR AU - ADENEYE, ADEJUWON AU - OLORUNDARE, OLUFUNKE AU - AKINSOLA, AKINYELE AU - SOYEMI, SUNDAY AU - MGBEHOMA, ALBAN AU - OKOYE, IKECHUCKWU AU - ALBRECHT, RALPH AU - NTAMBI, JAMES AU - MUKHTAR, HASAN PY - 2021/01/07 Y2 - 2024/03/29 TI - EXPERIMENTAL THERAPEUTIC EVALUATION OF THE AFRICAN VEGETABLES (CLERODENDRUM VOLUBILE LEAF AND IRVINGIA GABONENSIS SEED EXTRACTS) IN TRASTUZUMAB-MEDIATED HEPATO-RENAL DYSFUNCTION IN WISTAR RATS JF - Asian Journal of Pharmaceutical and Clinical Research JA - Asian J Pharm Clin Res VL - 14 IS - 1 SE - Original Article(s) DO - 10.22159/ajpcr.2021.v14i1.40118 UR - https://journals.innovareacademics.in/index.php/ajpcr/article/view/40118 SP - 147-157 AB - <p><strong>Objective: </strong>The use of trastuzumab (<em>TZM</em>) in the clinical management of human epidermal growth factor receptor 2 positive metastatic breast and gastric cancers, gastro-esophageal adenocarcinoma, and colorectal carcinoma has 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 at investigating the protective and therapeutic potentials of 400 mg/kg/day <em>Clerodendrum volubile </em>ethanol leaf extract (<em>CVE</em>) and <em>Irvingia gabonensis </em>ethanol seed extract (<em>IGE</em>) pretreatments in <em>TZM</em>-intoxicated Wistar rats based on their reported folkloric use in the local management of kidney and liver diseases and the previously reported therapeutic potential of these African vegetables in <em>TZM </em>cardiotoxicity.</p><p><strong>Methods: </strong>Forty-nine male Wistar rats were randomly allotted into seven groups of seven rats per group. Group I rats were treated with 10 ml/kg/day of 5% dimethyl sulfoxide (DMSO) sterile water <em>p.o. </em>and 1 ml/kg/day 5% DMSO sterile water <em>i.p.</em>; Groups II and III rats were orally pretreated with 400 mg/kg/day <em>CVE </em>and <em>IGE</em>, respectively, 3 h before 1 ml/kg/day/<em>i.p. </em>5% DMSO sterile water; Group IV rats were orally pretreated with 10 ml/kg/day 5% DMSO sterile water 3 h before 2.25 mg/kg/day/<em>i.p. TZM</em>; and Groups V-VII rats were pretreated with 20 mg/kg/day Vit. C, 400 mg/kg/day <em>CVE, </em>and 400 mg/kg/day <em>IGE </em>all dissolved in 5% DMSO sterile water, respectively, 3 h before <em>i.p. </em>injections of 2.25 mg/kg/day <em>TZM</em>, all for 7 days. Liver function parameters, renal function parameters, oxidative stress markers, and histopathological investigations were the study measuring endpoints.</p><p><strong>Results: </strong>Oral pretreatment with 20 mg/kg/day Vit. C, 400 mg/kg/day <em>CVE </em>and <em>IGE </em>significantly ameliorated <em>TZM</em>-mediated hepatic and renal toxicities by effectively lowering the serum alanine transaminase, aspartate transaminase, alkaline phosphatase, creatinine, and urea levels. <em>CVE </em>and <em>IGE </em>pretreatments also significantly reversed <em>TZM</em>-induced decreases in the hepatic and renal tissue catalase, superoxide dismutase, and glutathione- <em>S</em>-transferase activities and reduced malondialdehyde levels. <em>CVE </em>and <em>IGE </em>pretreatments also improved <em>TZM</em>-induced hepatic and renal histological lesions.</p><p><strong>Conclusions: </strong>Overall, the chemotherapeutic/chemopreventive potentials of <em>CVE </em>and <em>IGE </em>in <em>TZM</em>-induced hepatorenal dysfunction were either wholly or partly mediated through free-radical scavenging and antioxidant activities.</p> ER -