Protection of clozapine‐induced oxidative stress and mitochondrial dysfunction by kaempferol in rat cardiomyocytes

Abstract

Clozapine (CLZ) is unusually efficient in psychotic diseases. Nonetheless, its use is confined due to potentially life-threatening adverse events, including cardiotoxicity.Since the cardiotoxicity of CLZ is mediated through the generation of active metabolites, free radical, and inflammation. Here, we tested this hypothesis that kaempferol (KP) as antioxidant and anti-inflammatory agent could attenuate CLZ-induced mitochondrial/lysosomal and oxidative damages in rat ventricular cardiomyocytes. Rat ventricular cardiomyocytes were isolated by collagenase perfusion. Then isolated cardiomyocytes were simultaneously treated with different concentrations of KP (10, 20, and 50 μM) and CLZ (50 μM) for 4 h at 37 C. After 4 h of incubation, using by flow cytometry and biochemical evaluations, the parameters of cellular toxicity including: cell viability, reactive oxygen species (ROS) formation, mitochondria membrane potential (ΔΨm) collapse, lysosomal membrane integrity, malondialdehyde, and oxidized/reduced glutathione were analyzed. The results showed that CLZ (50 μM) induced a significant increase in cytotoxicity, ROS formation, mitochondrial membrane potential collapse, lipid peroxidation, and oxidative stress while KP reverted the above toxic effect of CLZ on isolated cardiomyocytes. Our data suggest that KP prevents and reverses CLZ-induced oxidative and mitochondrial/lysosomal damages in isolated cardiomyocytes, providing an experimental basis for clinical treatment on CLZ-induced cardiotoxicity.

Kaempferol attenuates inflammation in lipopolysaccharide‐induced gallbladder epithelial cells by inhibiting the MAPK/NF‐κB signaling pathway

“…This suggested that lower concentrations of KPR (up to 100 μM) did not impair the cellular integrity, while the 200 μM concentration induced toxicity, as evidenced by increased LDH release into the cell culture medium. Therefore, combined with the previous studies (Al Sabaani, 2020; Bakhshii et al., 2021; Kim et al., 2016), 50 μM KPR was selected as the optimal concentration for the following experiments.…”

Probing the Potential Mechanism of Quercetin and Kaempferol against Heat Stress-Induced Sertoli Cell Injury: Through Integrating Network Pharmacology and Experimental Validation

“…In the present study, quercetin and kaempferol protected testicular SCs from oxidative stress injury and improved their resistance to heat stress, which was consistent with previous studies [ 61 , 62 ]. Quercetin and kaempferol have a weak ability to improve SOD activity of heat-damaged supporting cells, but for flavonoid monomers, their antioxidant ability lies not only in improving the level of antioxidants, such as SOD but also in their unique active structure to prevent and eliminate oxygen free radicals [ 63 , 64 ]. Quercetin has one more ortho phenolic hydroxyl than kaempferol.…”

Advances in Research on Chemical Constituents and Their Biological Activities of the Genus Actinidia

“…8, Table 7). Pharmacological studies indicated that these compounds, particularly kaempferol and its derivative, had a wide range of biological activities including antiproliferation, antioxidation, anti-inflammation, anticancer, anti-free radical, and neuroprotection activities [96][97][98][99] 8). They were isolated from this plant for the first time [108].…”

“… 155 7,4′-Dihydroxyflavone A. chinensis Planch [ 105 ] Roots Anti-inflammatory (in vitro) [ 106 ] 156 Formononetin A. chinensis Planch [ 105 ] Roots 157 Kaempferol A . deliciosa [ 107 ] Leaves Antiproliferation human tumor cell (in vitro) [ 96 ] Antioxidant and anti-inflammatory (in vitro) [ 97 ] Anticancer (in vitro) [ 98 ] Neuroprotection (in vitro) [ 99 ] 158 6-C-Glucose-5,7,3′,4′-tetrahydroxy flavone A. arguta [ 108 ] Roots 159 6-C-Glucose-5,7,4′-trihydroxy flavone A. arguta [ 108 ] Roots 160 6-C-Glycopyranosyl-8-C-xyloeyl apigenin A. polygama [ 109 ] Leaves 161 Vicenin-I A. polygama [ 110 ] Aerial Parts 162 Kaempferol 3-O-glucoside A . deliciosa [ 107 ] Leaves 163 …”