Influence of Clerodendrum volubile leaf extract on doxorubicin-induced toxicity and inhibition of carbonyl reductase mediated metabolism

Abstract

Objectives Doxorubicin (DOX) is a commonly used chemotherapeutic drug. However, its non-target organ toxicities pose a serious problem. This study is to assess the protective role of Clerodendrum volubile leaf extract (CVE) against DOX-induced toxicities in rats. In addition, the inhibitory activities of three phytochemical compounds (Rutin, Gallic acid and Rosmarinic acid) from CVE against Carbonyl reductase 1 (CBR1) were examined. Methods Rats were randomly divided into 5 groups: (a) Control group rats were given 0.9% NaCl as vehicle, (b) DOX group: A single dose of DOX (25 mg/kg; i.p.) was administered and rats were sacrificed 4 days after DOX injection, while groups (c–e) CVE-treated DOX rat groups were given 125, 250 and 500 mg/kg body weight of extracts orally for 12 consecutive days; 8 days before, and 4 days after the DOX administration. Computational techniques were used to determine the inhibitory activities of the compounds against CBR1. Results DOX intoxication caused a significant increase (p<0.05) in serum marker enzymes: ALT, AST, ALP, LDH, CK activities. The levels of liver and heart tissues antioxidant parameters: GPx, SOD, CAT, and GSH were significantly (p<0.05) decreased in DOX-intoxicated rats with concomitant elevation of malondialdehyde levels. Pretreatment with CVE reversed the above trends. From the structural analysis, Rutin and RSA exhibited the highest binding free energies against CBR1, and also exhibited structural stability when bound with CBR1. Conclusions Our study indicates the protective effect of CVE when used in combination with doxorubicin thus improving its chemotherapeutic application via inhibition of CBR-mediated metabolism.

Protective effect of mangiferin on doxorubicin-induced liver damage in animal model

“…The administration of doxorubicin in this research has also significantly decreased the activities of superoxide dismutase (SOD) in the liver. This result is in line with the findings of other studies [6,22]. Similarly, the usage of doxorubicin can decrease protein content and cytosolic SOD enzyme activities by oxidating active sites or forming cross-link protein [3].…”

“…In the case of acute liver damages, the ALT escalates more significantly than the AST [18]. This result shows that the injection of doxorubicin damages liver cells, corresponding to the results of other studies [6,19].…”

“…In line with some findings in previous research [6,21,22], this study found a significant increase in the MDA level of induced rats both in plasma and liver tissue. The rise in MDA content proved that the administration of doxorubicin could result in oxidative stress.…”

“…The liver, an organ that plays a significant role in metabolism, could suffer damage due to the presence of doxorubicin. Some research shows that the damage of a liver is related to the inflammation process, free radicals, oxidative stress, and lipid peroxidation which all happen simultaneously due to the administration of doxorubicin [6]. The damage to various organs, including liver, due to the administration of doxorubicin is mediated by oxidative stress.…”