Esculetin and idebenone ameliorate galactose‐induced cataract in a rat model

Abstract

Cataract is the principal cause of blindness. The enzyme, aldose reductase (AR) is a key player in polyol pathway. Buildup of polyols and oxidative stress are the main causes of cataractogenesis. This study investigated the cytoprotective properties of esculetin and idebenone in galactose‐induced cataract. Rats were partitioned into four groups each of ten rats. Control group was fed with normal diet; group 2 rats were fed with galactose diet (50%); groups 3, 4 rats were fed with galactose diet concurrently with either esculetin (50 mg/kg BW) or idebenone (100 mg/kg BW), for 20 days. The study revealed that esculetin and idebenone significantly reduced the elevated levels of Bax/Bcl‐2 ratio, malondialdehyde, and DNA fragmentation and increased total antioxidant capacity level in lenses compared to the cataract‐induced group. Only esculetin decreased AR, galactitol, and advanced glycated end products levels in lenses. Histopathological examinations supported the biochemical findings. Esculetin and idebenone may have chemopreventive effects for sugar cataract. Practical applications Cataract is an age‐related disease that might cause blindness in older adult people. Presently, no absolute pharmacological treatment is accessible for cataract. The use of natural products or their derivatives attract particular attention in modern medicines as they are believed to be safer with few or no side effects. Esculetin is a polyphenolic compound found in many medicinal plants. Idebenone is a synthetic analogue of coenzyme Q10. The current study is an approach to explore the anticataract effects of esculetin and idebenone in galactose‐induced cataract in rats. Our study proved that both agents have anticataractogenic potentials due to their antioxidant and antiapoptotic properties.

Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy

“…In contrast to elamipretide and #37, #77 did not show a significant antioxidant effect, which suggests that the protection by #77 appears to involve mechanisms(s) distinct to the other compounds. Idebenone is widely portrayed as being a potent antioxidant [13] but, in the present study, there is no statistically significant antioxidant effect, which is in stark contrast to a previous report, where idebenone significantly reduced markers of oxidative damage in a rat model of cataract formation [39]. This effect was dependent on the route of administration and dose and, while the cataract study used oral idebenone (100 mg/kg), the present study used 10 mg/ml in eyedrops.…”

Idebenone regulates sirt1/Nrf2/TNF-α pathway with inhibition of oxidative stress, inflammation, and apoptosis in testicular torsion/detorsion in juvenile rats

“…That is in line with Gerhardt et al, 40 who found that IDE inhibited the activation of pro-apoptotic factors in mice. Sadik and her coworkers 41 also supported our results as they reported that IDE ameliorated galactose-induced cataracts in rats through its antioxidant and antiapoptotic properties.…”

Idebenone: When an antioxidant is not an antioxidant

“…In fact, several in vitro and in vivo studies suggest that idebenone appears to do exactly that. In a model of galactose-induced cataract formation idebenone reduced oxidative damage by increasing total endogenous tissue antioxidant capacity [ 56 ]. This increased antioxidant capacity by idebenone is likely the consequence of an increased expression of a range of endogenous antioxidants such as superoxide dismutase (SOD), catalase, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione (GSH), and glutathione peroxidase (GPx) [ 37 , 45 , 48 , 49 , 57 ], while also downregulating the superoxide-producing enzyme NOX2 [ 58 ].…”