Riboceine Regimen Attenuates Ethanol-induced Neuronal Damage in the Cerebellum of Adult Male Wistar Rats

Background: Although ethanol exerts its neurotoxic effect on the brain through inflammatory and oxidative processes, the effect of Riboceine on the brain following ethanol neurotoxicity is yet to be elucidated. Therefore, this study was designed to evaluate the effects of riboceine on the cellular, behavioral, and molecular impairments induced by ethanol toxicity in rats. Methods: A total of 24 male Wistar rats weighing between 160-170 grams were used for the study, and were divided into four groups of six rats each. After completion of the administration of ethanol and riboceine, and testing for motor impairment, the rats were sacrificed. The cerebellum was excised and processed for oxidative stress analyses, based on oxidative stress markers and histological examinations. The immunohistochemical expression of astrocytes in the cerebellum was examined, using Glial Fibrillary Acidic Protein (GFAP) stain. Results: This study demonstrated that ethanol-induced neurotoxicity in the cerebellum, characterized by increased oxidative stress profile, astrocyte activation, and neuronal death in the cerebellum, especially the Purkinje layer. Necrosis, significant decrease in Superoxide Dismutase (SOD), Catalase (CAT) and Gluathione (GSH) activities (P<0.05) as well as astrogliosis was associated with ethanol treatment. However, riboceine was observed to significantly increase the cerebellar SOD, CAT and GSH activities with significantly reduced Malondialdehyde (MDA) levels (P<0.05). It also attenuated the histomorphological alteration of the cerebellum and reduced the cerebellar astrocytes activation following ethanol-induced neurotoxicity, thus leading to the attenuation of motor impairment. Conclusion: Riboceine attenuated motor impairment caused by chronic ethanol-induced neurotoxicity, suggestive of its anti-oxidative and anti-inflammatory properties.

[1]  A. Ajayi,et al.  D-ribose-L-cysteine enhances memory task, attenuates oxidative stress and acetyl-cholinesterase activity in scopolamine amnesic mice. , 2020, Drug development research.

[2]  S. Cuzzocrea,et al.  Astrocytes: Role and Functions in Brain Pathologies , 2019, Front. Pharmacol..

[3]  D. Głąbska,et al.  Influence of Alcohol Consumption on Body Mass Gain and Liver Antioxidant Defense in Adolescent Growing Male Rats , 2019, International journal of environmental research and public health.

[4]  R. Prediger,et al.  Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats , 2018, Front. Behav. Neurosci..

[5]  R. Meurer,et al.  Morphological changes in the cerebellum as a result of ethanol treatment and cigarette smoke exposure: A study on astrogliosis, apoptosis and Purkinje cells , 2018, Neuroscience Letters.

[6]  K. Rauf,et al.  Neuroprotective effect of Bacopa monnieri against morphine-induced histopathological changes in the cerebellum of rats. , 2017, Pakistan journal of pharmaceutical sciences.

[7]  Benedict A. Falana,et al.  Effect of D-ribose-L-cysteine on aluminum induced testicular damage in male Sprague-Dawley rats , 2017, JBRA assisted reproduction.

[8]  O. Oguntibeju,et al.  Hepato- and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats , 2016, Toxicology reports.

[9]  R. Prediger,et al.  Chronic Ethanol Exposure during Adolescence in Rats Induces Motor Impairments and Cerebral Cortex Damage Associated with Oxidative Stress , 2014, PloS one.

[10]  Y. Yanagawa,et al.  Motor dysfunction in cerebellar Purkinje cell-specific vesicular GABA transporter knockout mice , 2014, Front. Cell. Neurosci..

[11]  Winfried Ilg,et al.  Gait ataxia—specific cerebellar influences and their rehabilitation , 2013, Movement disorders : official journal of the Movement Disorder Society.

[12]  Mahmoud Elahdadi Salmani,et al.  Role of Oxidative Stress in Ethanol-induced Neurotoxicity in the Developing Cerebellum , 2012, Iranian journal of basic medical sciences.

[13]  J. Weber,et al.  The role of calcium in synaptic plasticity and motor learning in the cerebellar cortex , 2012, Neuroscience & Biobehavioral Reviews.

[14]  V. Lobo,et al.  Free radicals, antioxidants and functional foods: Impact on human health , 2010, Pharmacognosy reviews.

[15]  Jun Ren,et al.  Alcohol Dehydrogenase Accentuates Ethanol-Induced Myocardial Dysfunction and Mitochondrial Damage in Mice: Role of Mitochondrial Death Pathway , 2010, PloS one.

[16]  Xiaoning Yang,et al.  Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury. , 2008, World journal of gastroenterology.

[17]  M. Pistis,et al.  Alcohol inhibits spontaneous activity of basolateral amygdala projection neurons in the rat: involvement of the endocannabinoid system. , 2008, Alcoholism, clinical and experimental research.

[18]  E. Faustman,et al.  Computational models of ethanol-induced neurodevelopmental toxicity across species: Implications for risk assessment. , 2008, Birth defects research. Part B, Developmental and reproductive toxicology.

[19]  L. Granero,et al.  Brain metabolism of ethanol and alcoholism: an update. , 2007, Current drug metabolism.

[20]  R. Olsen,et al.  Low dose acute alcohol effects on GABA A receptor subtypes. , 2006, Pharmacology & therapeutics.

[21]  D. K. Williams,et al.  Purkinje cell vulnerability to developmental ethanol exposure in the rat cerebellum. , 1999, Alcoholism, clinical and experimental research.

[22]  J. Labandeira-Garcia,et al.  An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism. , 1997, Brain research. Brain research protocols.

[23]  D. Pitt Histochemical Demonstration of Certain Hydrolytic Enzymes within Cytoplasmic Particles of Botrytis cinerea Fr. , 1968 .

[24]  A. Majid,et al.  NEUROPROTECTIVE EFFECTS OF AQUEOUS DATE FRUIT EXTRACT ON FOCAL CEREBRAL ISCHEMIA IN RATS , 2008 .

[25]  E. Skrzydlewska,et al.  [The action of oxidative stress induced by ethanol on the central nervous system (CNS)]. , 2005, Postepy higieny i medycyny doswiadczalnej.

[26]  D. Butterfield,et al.  Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: protection by acetyl carnitine. , 2002, International journal of tissue reactions.