African Vegetables (Clerodendrum volubile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats

Olorundare, Olufunke E.; Adeneye, Adejuwon Adewale; Akinsola, Akinyele Olubiyi; Soyemi, Sunday Sokunle; Mgbehoma, Alban Ikenna; Okoye, Ikechukwu Innocent; Ntambi, James M.; Mukhtar, Hasan

doi:10.1155/2020/9535426

Cited by 11 publications

(14 citation statements)

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Section: Discussionmentioning

confidence: 50%

“…TZM is known to cause related cardiac dysfunction without corresponding histoarchitectural distortion of the myocytes ( Jones et al, 2009 ) although TZM was recently reported to induce severe vascular congestion and associated microthrombi formation ( Olorundare et al, 2020 ) in treated experimental rats which the present study is in tandem with. However, the fact that these histopathological changes were profoundly improved by ADP, VAL, and fixed-dose (ADP + VAL) combination pretreatments strongly suggests the cardioprotective potential of these drugs.…”

Section: Discussionmentioning

confidence: 54%

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Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity

et al. 2021

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Trastuzumab (TZM) is useful in the clinical management of HER2-positive metastatic breast, gastric, and colorectal carcinoma but has been limited by its off-target cardiotoxicity. This study investigates the therapeutic potentials of 0.25 mg/kg/day amlodipine, 0.035 mg/kg/day lisinopril, 5 mg/kg/day valsartan, and their fixed-dose combinations in TZM-intoxicated Wistar rats that were randomly allotted into 10 groups of 6 rats for each group. Group I rats were treated with 10 ml/kg/day sterile water orally and 1 ml/kg/day sterile water intraperitoneally; Groups II, III, and IV rats were orally gavaged with 5 mg/kg/day valsartan and 1 ml/kg/day sterile water intraperitoneally, 0.25 mg/kg/day amlodipine and 1 ml/kg/day sterile water via the intraperitoneal route, 0.035 mg/kg/day lisinopril and 1 ml/kg/day sterile water administered intraperitoneally, respectively. Group V rats were orally treated with 10 ml/kg/day of sterile water prior to intraperitoneal administration of 2.25 mg/kg/day of TZM. Groups VI–VIII rats were equally pretreated with 5 mg/kg/day valsartan, 0.25 mg/kg/day amlodipine, and 0.035 mg/kg/day lisinopril before intraperitoneal 2.25 mg/kg/day TZM treatment, respectively; Groups IX and X rats were orally pretreated with the fixed-dose combinations of 0.25 mg/kg/day amlodipine +0.035 mg/kg/day lisinopril and 5 mg/kg/day valsartan +0.035 mg/kg/day lisinopril, respectively, before TZM treatment. Cardiac injury and tissue oxidative stress markers, complete lipids profile, histopathological, and immunohistochemical assays were the evaluating endpoints. Results showed that repeated TZM treatments caused profound increases in the serum TG and VLDL-c levels, serum cTnI and LDH levels, and cardiac tissue caspase-3 and -9 levels but decreased BCL-2 expression. TZM also profoundly attenuated CAT, SOD, GST and GPx activities, and increased MDA levels in the treated tissues. In addition, TZM cardiotoxicity was characterized by marked vascular and cardiomyocyte congestion and coronary artery microthrombi formation. However, the altered biochemical, histopathological, and immunohistochemical changes were reversed with amlodipine, lisinopril, valsartan, and fixed-dose combinations, although fixed-dose valsartan/lisinopril combination was further associated with hyperlipidemia and increased AI and CRI values and coronary artery cartilaginous metaplasia. Thus, the promising therapeutic potentials of amlodipine, lisinopril, valsartan and their fixed-dose combinations in the management of TZM cardiotoxicity, majorly mediated via antiapoptotic and oxidative stress inhibition mechanisms were unveiled through this study.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 54%

Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity

et al. 2021

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“…The extraction processes of the fresh leaves of C. volubile and pulverized I. gabonensis seeds and their % yields calculated as described by Olorundare et al [58].…”

Section: Extraction Processesmentioning

confidence: 99%

“…In addition, ranolazine a new anti-ischemia drug and, a specific and potent late sodium current inhibitor, has been reported to attenuate TZM-induced cardiac dysfunction which is known to mediate its action through inhibition of reactive oxygen species (ROS) production [56] and upregulation of antioxidant enzymes [57]. Recently, we reported the protective effect of C. volubile ethanol leaf and I. gabonensis ethanol seed extracts against TZM-induced cardiotoxicity in rats [58]. However, there are no effective antidotes to TZM-mediated hepatorenal toxicities reported so far.…”

Section: Introductionmentioning

confidence: 99%

Experimental Therapeutic Evaluation of the African Vegetables (Clerodendrum Volubile Leaf and Irvingia Gabonensis Seed Extracts) in Trastuzumab-Mediated Hepato-Renal Dysfunction in Wistar Rats

Adeneye

Olorundare

Akinsola

et al. 2021

Asian J Pharm Clin Res

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Objective: The use of trastuzumab (TZM) 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 Clerodendrum volubile ethanol leaf extract (CVE) and Irvingia 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 the previously reported therapeutic potential of these African vegetables in TZM cardiotoxicity. Methods: 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 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 h 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 h before 2.25 mg/kg/day/i.p. TZM; and 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 h 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 phosphatase, creatinine, and urea levels. CVE and IGE pretreatments also significantly reversed TZM-induced decreases in the hepatic and renal tissue catalase, superoxide dismutase, and glutathione- S-transferase activities and reduced malondialdehyde levels. CVE and IGE pretreatments also improved TZM-induced hepatic and renal histological lesions. Conclusions: Overall, the chemotherapeutic/chemopreventive potentials of CVE and IGE in TZM-induced hepatorenal dysfunction were either wholly or partly mediated through free-radical scavenging and antioxidant activities.

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“…In the study of Olorundare and co-workers [ 125 ], they observed that the extract was able to ameliorate the cardiac tissue oxidative stress markers in the studied rats through an antioxidant mechanism by scavenging the free radicals generated by DOX toxicity. Similarly, in another study investigated by Olorundare and colleagues, for the first time, ethanolic extract of C. volubile leaves significantly decreased trastuzumab (TZM)-induced cardiotoxicity in rats, and its cardioprotective effect was recorded to be facilitated through its antioxidant ability, which stimulates free radical scavenging and inhibits lipid peroxidation [ 127 ]. Also, Adeneye et al [ 128 ] confirmed the protective and therapeutic potentials of ethanolic extract of C. volubile leaves in trastuzumab-intoxicated Wistar rats.…”

Section: Pharmacological Potentials Of C Volubilementioning

confidence: 99%

Traditional Uses, Nutritional and Pharmacological Potentials of Clerodendrum volubile

Okaiyeto

Falade

Oguntibeju

2021

Plants

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Clerodendrum volubile is an underutilized leafy vegetable consumed in some parts of Nigeria. The interest in C. volubile has continued to increase due to its multipurpose values, including traditional uses, nutritional properties, and some therapeutic potentials; however, the pharmacological prospects of the plant are yet to be fully explored. Therefore, in the present review, different databases such as PubMed, Scopus, Web of Science, Google Scholar, etc. were explored to retrieve publications used to write this review. The pharmacological potentials of C. volubile, such as anticancer, antioxidant, antiviral, antimicrobial, anti-inflammatory, hepatoprotective, antidiabetic, and anti-hypertensive properties, were highlighted. The toxicological potential of the plant is also discussed. Proposed mechanisms that underline its biological activities include modulation of redox homeostasis, leading to decreased oxidative stress; down-regulation of matrix metalloproteinase-9 (MMP-9) expression; inhibition of key enzymes implicated in diabetes mellitus, hypertension, and neurological diseases; and inhibition of oxidative burst and inflammatory cytokines. Furthermore, the prospect of endophytes from C. volubile as a bioresource to produce novel therapeutic agents, as well as the development of nanotherapeutics from the plant extracts and its phytoconstituents, are discussed. In conclusion, C. volubile possesses an enormous number of possible pharmacological properties and therapeutic potentials waiting to be explored.

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African Vegetables (Clerodendrum volubile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats

Cited by 11 publications

References 100 publications

Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity

Therapeutic Potentials of Selected Antihypertensive Agents and Their Fixed-Dose Combinations Against Trastuzumab-Mediated Cardiotoxicity

Experimental Therapeutic Evaluation of the African Vegetables (Clerodendrum Volubile Leaf and Irvingia Gabonensis Seed Extracts) in Trastuzumab-Mediated Hepato-Renal Dysfunction in Wistar Rats

Traditional Uses, Nutritional and Pharmacological Potentials of Clerodendrum volubile

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