Morin Hydrate Mitigates Cisplatin‐Induced Renal and Hepatic Injury by Impeding Oxidative/Nitrosative Stress and Inflammation in Mice

Abstract

Cisplatin is a widely used chemotherapeutic drug; however, it induces damage on kidney and liver at clinically effective higher doses. Morin hydrate possesses antioxidant, anti-inflammatory, and anticancer properties. Therefore, we aimed to investigate the effects of morin hydrate (50 and 100 mg/kg, orally) against the renohepatic toxicity induced by a high dose of cisplatin (20 mg/kg, intraperitoneally). Renal and hepatic function, oxidative/nitrosative stress, and inflammatory markers along with histopathology were evaluated. Morin hydrate ameliorated cisplatin-induced renohepatic toxicity significantly at 100 mg/kg as evidenced from the significant reversal of cisplatin-induced body weight loss, mortality, functional and structural alterations of kidney, and liver. The protective role offered by morin hydrate against cisplatin-induced renohepatic toxicity is by virtue of its free radical scavenging property, thereby abating the depletion of cellular antioxidant defense components and through modulation of inflammatory cytokines. We speculate morin hydrate as a protective candidate against renohepatic toxicity of cisplatin.

Astragaloside IV protects against cisplatin-induced liver and kidney injury via autophagy-mediated inhibition of NLRP3 in rats

“…However, the adverse events associated with cisplatin treatment, which occur in 28% to 36% of patients, limit its efficacy, many times resulting in the prolongation of treatment cycles. The kidneys and the liver are two of the organs where cisplatin accumulates, frequently leading to nephrotoxicity and hepatotoxicity (Gao et al, 2017;Isoda et al, 2018;K v et al, 2016). Moreover, the toxicity profile of cisplatin significantly reduces patient survival and quality of life.…”

Morin decreases galectin-3 expression and sensitizes ovarian cancer cells to cisplatin

“…Compensation of these adverse effects can be achieved by combination treatment with a drug, which would reduce the systemic toxicity by acting as an antioxidant or by allowing to decrease the required dose of chemotherapeutic agent [24]. In fact, it has been proven that morin treatment along with cisplatin significantly mitigated the negative influence of cisplatin on liver [37] and kidney function [7, 37, 38], through the reduction of oxidative stress, inflammation and apoptosis [7]. On the other hand, we (along with many others) have demonstrated that morin sensitizes various cancer cells to chemotherapeutic agents, what may allow to decrease the required doses in clinical treatment in the future.…”

“…Second , this is not the only possible action of morin inside cells. This flavonol also acts as an antioxidant, which reduces oxidative stress [7, 37]. The activity may be achieved due to the presence of the hydroxyl groups attached at various positions in its characteristic flavonoid structure, which can directly scavenge the reactive species [38].…”

“…The activity may be achieved due to the presence of the hydroxyl groups attached at various positions in its characteristic flavonoid structure, which can directly scavenge the reactive species [38]. Nonetheless, the anti-oxidative nature of morin results in sparing of cellular antioxidants, such as glutathione and in vivo study showed that pre-treatment with morin increased tissue GSH level [37, 38]. Moreover, an increased glutathione (a nucleophilic molecule) concentration neutralizes cisplatin before its binding with the DNA, and this leads to cisplatin-resistance [39].…”

Anti-Inflammatory Effect of a TCM Formula Li-Ru-Kang in Rats With Hyperplasia of Mammary Gland and the Underlying Biological Mechanisms

“…We found 19 potential compounds, including saikosaponin c_qt, quercetin, kaempferol and chrysazin, Luteolin, beta-sitosterol, isorhamnetin, curcolactone, stigmasterol, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol, areapillin, morin, 3,5,6,7-tetramethoxy-2-(3,4,5-trimethoxyphenyl) chromone, delphinidin, troxerutin, cubebin, α-spinasterol, linoleyl acetate and vulgaxanthin-I might play the key role in LRK-treated HMG. Studies showed that most of those potential active ingredients have anti-inflammatory or anti-oxidative effects, such as quercetin, ( Song et al, 2018 , kaempferol ( Huang et al, 2018 ; Wang J. et al, 2018 ), Luteolin ( Aziz et al, 2018 ), beta-sitosterol ( Liao et al, 2018 ), isorhamnetin ( Qiu et al, 2016 ), delphinidin ( Wang et al, 2017 ), troxerutin ( Najafi et al, 2018 ), cubebin ( Bastos et al, 2001 ), morin ( Athira et al, 2016 ), linoleyl acetate ( Peana et al, 2002 ) have anti-inflammatory effects. Compounds like quercetin ( Sherif, 2018 ), kaempferol ( Kouhestani et al, 2018 ), Luteolin ( Yang et al, 2018 ), beta-sitosterol ( Yin et al, 2018 ), delphinidin ( Cheol et al, 2016 ), troxerutin ( Farajdokht et al, 2017 ), morin ( Ma et al, 2016 ), linoleyl acetate ( Peng et al, 2014 ) showed anti-oxidative stress effect.…”