The Possible Protective Role of Ginger Extract Versus Vitamin E Against Simvastatin-Induced Skeletal Myotoxicity in Adult Male Albino Rats: Histological, Physiological and Biochemical Study

Abstract

Introduction: Statins are group of drugs used to reduce total and low density lipoprotein (LDL)-cholesterol level and to reduce the morbidity and mortality of cardiovascular diseases. Meanwhile, induced skeletal muscle-specific mitochondrial impairment, oxidative stress and myotoxicity are serious side effects . Vitamin E and ginger extract are well known potent antioxidants. Aim: To study the possible protective effect of ginger extract versus vitamin E against simvastatin-induced skeletal muscle histological and the associated biophysiological changes. Materials and Methods: Forty adult male albino rats were randomly divided into four equal groups (10 rats, each).; Group 1: was the control rats. Group 2: received 0.54 mg/kg/day simvastatin orally for 8 weeks. Group 3: received concomitant treatment of simvastatin and 30 mg/kg/day vitamin E orally for 8 weeks. Group 4 received concomitant treatment of simvastatin and 500mg/kg/day ginger extract orally for 8 weeks. After sacrifice, specimens were taken from the belly of the quadriceps femoris muscles of all animal groups and processed for light and electron microscopy. Biochemical tests and statistical analysis were done. Results: Group 2 showed focal areas of muscle fiber loss, mononuclear cellular infiltration and variable staining density. Ultra structurally, myofibrillar degeneration and accumulation of numerous giant infrequently damaged mitochondria were observed. The skeletal muscle fibers of animals from group 3 and group 4, both were markedly improved. Group 4 revealed obviously normal mitochondria. Conclusion: Administration of simvastatin for 8 weeks induced histological, physiological and biochemical skeletal myotoxic effects. These effects were greatly ameliorated by concomitant administration vitamin E or ginger extract. Ginger extract was more effective.

Ginger Supplementation Attenuated Mitochondrial Fusion and Improved Skeletal Muscle Size in Type 2 Diabetic Rats

“…Additionally, mitochondrial fission (DRP-1 mRNA) trended (p=0.067, Cohen's d=0.45) to be lower in diabetic rats with ginger supplementation. Kawther et al reported that following statin-induced ROS, mitochondria exhibit morphology consistent with unhealthy mitochondria (that is, accumulation of giant mitochondria with destructed cristae) (36). However, in the same study when statins were given ginger supplementation, ginger attenuated statin-induced ROS and improved mitochondrial health (that is, normal sized mitochondria with intact cristae) (36).…”

“…Ginger supplementation scavenges O 2 -(29-31) and has been shown to attenuate muscle atrophy in chemically-induced atrophy rodent models (36,37). Accumulation of oxidative stress (i.e., O 2 -, H 2 O 2 ) results in cellular damage (46), leading to muscle atrophy (7-9, 11, 47).…”

“…In individuals with type 2 diabetes, ginger supplementation decreased serum concentration of malondialdehyde [that is, a measure of ROS (34,35)]. In chemically-induced muscle damage and aging rodent models, ginger supplementation attenuated DNA and mitochondria damage (that is, markers of reduced oxidative stress) (36,37).…”

“…Oxidative stress and disrupted mitochondrial dynamics contribute to skeletal muscle atrophy in diabetic models (7,24). Ginger supplementation has been shown to reduce circulating oxidative stress in individuals with type 2 diabetes (35) as well as attenuate mitochondrial damage in aged and chemically-induced muscle damage rodent models, but not in type 2 diabetic models (36,37). Therefore, the purpose of the current study was to examine the effects of GRE on intramuscular oxidative stress, mitochondrial dynamics, and muscle size in type 2 diabetic rats.…”

Ginger (Zingiber officinale) Root Capsules Enhance Analgesic and Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation

“…A more precise biomarker reflecting oxidative stress is the OSI pro-oxidant marker, which can reflect an imbalance between antioxidants and pro-oxidation levels as it is defined as the ratio of the TOS level to the TAC level [ 74 ]. Ginger can influence the TAC and TOS ratio and therefore reduce the OSI index through the prevention of oxidation and nitration reactions induced by peroxynitrite, inhibition of xanthine oxidase responsible for the generation of reactive oxygen species, such as superoxide anion or inhibition of NO synthesis [ 75 ].…”