Coenzyme Q10 nullified khat-induced hepatotoxicity, nephrotoxicity and inflammation in a mouse model

Abstract

The consumption of khat (Catha Edulis, Forsk) is on the rise despite the much publicized associated deleterious health effects. How chemicals present in khat, affect various physiological and biochemical processes requires further scrutiny. A clear understanding of these processes will provide an avenue for countering khat-driven negative effects using appropriate pharmacological and/or nutritional interventions.Aim of the study: The current study investigated the effect of khat on vital physiological and biochemical processes such as oxidative stress, inflammation and immune responses and the role of Coenzyme-Q 10 (CoQ 10 ), a potent antioxidant and anti-inflammatory, in modulating any negative effects due to khat exposure. Methodology: Three (3) weeks old forty (40) Swiss albino mice were randomly assigned into four treatment groups (n ¼ 10). The first group was the control that was not administered with khat or CoQ 10 . The second group received 200 mg/kg body weight (b/w) of CoQ 10 , while the third group received 1500 mg/kg b/w of khat extract and finally the forth group was co-treated with 200 mg/kg b/w of CoQ 10 and 1500 mg/kg b/w of khat extract. The experiment was conducted for 90 days after which samples were collected for physiological and biochemical analyses.Results: The effects of khat and CoQ 10 on the weights of brain, liver, kidney and spleen was determined. Administration of khat decreased the levels of RBCs and its subtypes (MCV, MCH, RDW-SD and RDW-CV), a clear indicator of khat-induced normochromic microcytic anemia. White blood cells (lymphocytes, monocytes, neutrophils and eosinophil) which are vital in responding to infections were markedly elevated by khat. Moreover, these results provide evidence for khat-induced liver and kidney injury as shown by increased biomarkers; AST, ALT, GGT and creatinine respectively. Standard histopathological analysis confirmed this finding for khat-driven liver and kidney injury. Further studies showed evidence for khat-induced inflammation and oxidative stress as depicted by increased levels of the pro-inflammatory cytokine TNF-alpha and elevation of GSH in the brain, liver and spleen. Remarkably, this is the first study to demonstrate the potential of CoQ 10 in ameliorating khat-induced negative effects as outlined. CoQ 10 supplementation restored the khat-induced reduction in RBC subtypes, and was protective against liver and kidney injury as shown by the appropriate biomarkers and standard histopathology analysis. The other significant finding was the CoQ 10 -driven normalization of GSH and TNF-α levels, indicating a protective effect from khat-driven oxidative stress and inflammation respectively. Conclusion: From this study, we conclude that CoQ 10 may be useful in nullifying khat-driven deleterious events among chronic khat users.

Effect of amphotericin B‐deoxycholate (Fungizone) on the mitochondria of Wistar rats' renal proximal tubules cells

“…This is in accordance with other data that showed the nephron‐protective effect of Co‐Q10 as respiratory substrate, antioxidant, and anti‐inflammatory agent. Co‐Q10 was shown previously to improve cisplatin and khat‐driven kidney oxidative stress and inflammation in rats (Kennedy et al, 2020; Khalifa et al, 2020) In addition, Co‐Q10 was reported to improve mitochondrial dysfunction of tacrolimus‐induced kidney failure (Yu et al, 2019).…”

A glyphosate-based herbicide disrupted hematopoiesis and induced organ toxicities, ameliorated by vitamin B12 in a mouse model

“…Furthermore, depletion of hemoglobin in the current study, possibly confirmed a decrease in RBCs which is consistent with the elevation of the total bilirubin level in the plasma; perhaps due to GBH-induced hemolysis. Reduction of GSH and increased lipid peroxidation of RBCs has been reported to result in cellular lysis ( Kennedy et al, 2020 , Jasper et al, 2012 ).…”

Molecular mechanisms underlying the renal protective effects of coenzyme Q10 in acute kidney injury

“…Since CoQ10 has been shown to have potent antioxidant and anti-inflammatory effects, Kennedy et al. [ 52 ] investigated the exact roles of CoQ10 in khat-induced AKI and found that CoQ10 (200 mg/kg, orally) significantly decreased creatinine levels and reduced tubular necrosis and tubular epithelium injury. The protective effect derived from CoQ10 might be associated with the reduction of oxidative stress and inflammation…”

“… 30 mg/kg, orally NA CoQ10 could not alleviate diclofenac-induced renal injury, but worsened impaired renal function Kennedy et al. 2020 [ 52 ] Mice Khat-induced nephrotoxicity (1500 mg/kg, gastric gavage) 200 mg/kg, orally Normalization of GSH and TNF-α expression CoQ10 decreased creatinine levels and reduced tubular necrosis and tubular epithelium injury Megrin et al. 2020 [ 53 ] Rats Lead-acetate-induced renal injury 10 mg/kg, intraperitoneally Upregulation Nrf2/HO-1 pathway CoQ10 reduced the deleterious cellular side effects of lead acetate exposure owing to its antioxidant, anti-inflammatory, and anti-apoptotic effects Abdeen et al.…”