Effect of Stanozolol and/or Cannabis Abuse on Hypertrophic Mechanism and Oxidative Stress of Male Albino Rat Cardiac Tissue in Relation to Exercise: A Sport Abuse Practice.

Adolescents commonly co-abuse many drugs including anabolic androgenic steroids either they are athletes or non-athletes. Stanozolol is the major anabolic used in recent years and was reported grouped with cannabis. The current study aimed at evaluating the biochemical and histopathological changes related to the hypertrophic effects of stanozolol and/or cannabis whether in condition of exercise practice or sedentary conditions. Adult male Wistar albino rats received either stanozolol (5 mg/kg, s.c), cannabis (10 mg/kg, i.p.), and a combination of both once daily for two months. Swimming exercise protocol was applied as a training model. Relative heart weight, oxidative stress biomarkers, cardiac tissue fibrotic markers were evaluated. Left ventricular morphometric analysis and collagen quantification was done. The combined treatment exhibited serious detrimental effects on the heart tissues. It increased heart tissue fibrotic markers (Masson's trichrome stain (p < 0.001), cardiac COL3 (p < 0.0001), and VEGF-A (p < 0.05)), lowered heart glutathione levels (p < 0.05) and dramatically elevated oxidative stress (increased malondialdehyde (p < 0.0001) and 8-OHDG (p < 0.0001)). Training was not ameliorating for the observed effects. Misuse of cannabis and stanozolol resulted in more hypertrophic consequences of the heart than either drug alone, which were at least largely assigned to oxidative stress, heart tissue fibrotic indicators, histological alterations, and morphometric changes.

Neuroprotective and cognitive enhancing effects of herbecetin against thioacetamide induced hepatic encephalopathy in rats via upregulation of AMPK and SIRT1 signaling pathways.

Acute liver injury, there is a risky neurological condition known as hepatic encephalopathy (HE). Herbacetin is a glycosylated flavonoid with many pharmacological characteristics. The purpose of this study was to assess the ability of herbacetin to protect against the cognitive deficits associated with thioacetamide (TAA) rat model and delineate the underlying behavioral and pharmacological mechanisms. Rats were pretreated with herbacetin (20 and 40 mg/kg) for 30days. On 30th day, the rats were injected with TAA (i.p. 350 mg/kg) in a single dose. In addition to a histpathological studies, ultra-structural architecture of the brain, liver functions, oxidative stress biomarkers, and behavioral tests were evaluated. Compared to the TAA-intoxicated group, herbacetin improved the locomotor and cognitive deficits, serum hepatotoxicity indices and ammonia levels. Herbacetin reduced brain levels of malodialdeyde, glutamine synthetase (GS), tumor necrosis factor- alpha (TNF-α), interleukin 1 B (IL-1ß), annexin v, and increased brain GSH, Sirtuin 1 (SIRT1), and AMP-activated kinase (AMPK) expression levels. Also, herbacetin improve the histopathological changes and ultra- structure of brain tissue via attenuating the number of inflammatory and apoptotic cells. Herbacetin treatment significantly reduced the toxicity caused by TAA. These findings suggest that herbacetin might be taken into account as a possible neuroprotective and cognitive enhancing agent due to its ability to reduce oxidative stress, inflammation and apoptosis associated with TAA.

Febuxostat attenuates aluminum chloride-induced hepatorenal injury in rats with the impact of Nrf2, Crat, Car3, and MNK-mediated apoptosis.

Aluminum (Al) is a ubiquitous xenobiotic with known toxicity for both humans and animals. Our study was conducted to investigate the protective role of febuxostat (Feb) against aluminum chloride (AlCl3)-induced hepatorenal injury in rats. Hepatorenal injury was induced by oral administration of AlCl3 (40 mg/kg b.w.), for 2 months. Twenty-four male Sprague-Dawley rats were randomly allocated into four groups (six rats/group). The first group received the vehicle thought the experiment. The second group was considered as a control positive group. The third and fourth groups received oral treatment of Feb (10 mg/kg.b.w.) and (15 mg/kg.b.w.), respectively with AlCl3, concurrently for 2 months. Twenty-four hours, after the last treatment, serum biochemical, molecular, histopathology, and immunohistochemical studies were evaluated. Our findings showed that rats intoxicated with Alcl3 had disturbed biochemical picture. In addition, intoxication with AlCl3 increased oxidative stress and apoptosis, as demonstrated by an increase in malodialdeyde (MDA), carnitine o-acetyltransferase (Crat), and carbonic anhydrase (Car3) with a decrease in glutathione (GSH), MAP kinase-interacting serine/threonine kinase (MNK) and nuclear factor-erythroid 2-related factor 2 (Nrf2) mRNA expression. Furthermore, the levels of tumor necrosis factor-alpha (TNF-α) and the levels of caspase-3 were elevated with sever hepatic and renal pathological changes. Conversely, Feb (15 mg/kg.b.w.) could improve the serum biochemical indices and repressed MDA, Crat, and Car3 levels, whereas it increased GSH, MNK, and Nrf2 levels. Feb inhibited the apoptotic effect of AlCl3 in the liver and kidney by decreasing caspase-3 and TNF-α expression. The protective effect of Feb against AlCl3 toxicity was confirmed by histopathological findings. Moreover, molecular docking studies supported the anti-inflammatory effect of Feb due to its significant binding interactions with cyclooxygenase-1 (COX-1), NF-kappa-B-inducing kinase (NIK), and mitogen-activated protein kinases-p38 (MAPK-p38). The findings suggest that Feb system Feb can avert Alcl3-induced hepatotoxicity and nephrotoxicity by enhancing the antioxidant defense system, and inhibiting the inflammatory cascade and apoptosis.

In vivo assessment of inflammatory cytokines induced oxidative stress signalling, and troponin I gene dysregulation in cardiac tissue associated with chronic administration of boldenone and tramadol, alone or in combination.

INTRODUCTION: The risk of cardiotoxicity is associated with the use of anabolic-androgenic steroids and analgesics, several deaths were attributed to such medications. OBJECTIVES: This study investigates the effects of boldenone (BOLD) and tramadol (TRAM) alone or in combination on the heart. MATERIAL AND METHODS: Forty adult male rats were divided into four groups. Normal control group, BOLD (5 mg/kg, i.m.) per week, tramadol Hcl (TRAM) (20 mg/kg, i.p.) daily and a combination of BOLD (5 mg/kg) and TRAM (20 mg/kg), respectively for two months. Serum and cardiac tissue were extracted for determination of serum, aspartate aminotransferase (AST), creatine phosphokinase (CPK) and lipid profiles, tissue malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and histopathological examination. Troponin I gene expression was quantified in cardiac tissue using real-time polymerase chain reaction technique. RESULTS: Groups received BOLD and TRAM alone and in combination showed elevated serum biochemical parameters (AST, CPK) and deviations in lipid profiles, elevation in oxidative and inflammatory parameters (MDA, NO, TNF-α and IL-6), and decrease in GSH and SOD, up-regulated cardiac troponin I as well as distorted cardiac histopathological pictures. CONCLUSION: The current study elucidated the risk of administration of these drugs for sustained periods as well as the marked detrimental effects of using these drugs in combination.

The Behavioral and Neurochemical Changes Induced by Boldenone and/or Tramadol in Adult Male Rats.

Boldenone and tramadol are abused among large sectors of adolescents. Therefore, the behavioral changes concerned with memory and cognitive functions and neurochemical variations were investigated in the cortex of rats treated with boldenone and/or tramadol. Rats were divided into control and rats treated with boldenone, tramadol, or both drugs. At the end of the treatment period, the memory and cognitive functions were evaluated by the Y-maze test (YMT) and elevated plus maze test (EPMT) and the motor activity was determined by the open field test (OFT). The cortex was dissected to carry out the neurochemical analyses. Rats treated with boldenone and/or tramadol showed impaired memory and cognitive functions and reduced motor activity. A significant increase in lipid peroxidation (MDA), nitric oxide (NO), and a significant decrease in reduced glutathione (GSH) were observed in the cortex of rats treated with boldenone and/or tramadol. The levels of acetylcholinesterase (AChE) and monoamine oxidase (MAO) decreased significantly. Western blot data showed a significant decrease in Bcl2 and a significant increase in caspase-3 and inducible nitric oxide synthase (iNOS) in rats treated with boldenone and/or tramadol. These changes were associated with neuronal death as indicated from the histopathological examination.The present findings indicate that boldenone and/or tramadol induced impairment in memory and cognitive functions. These changes could be mediated by the increase in oxidative stress, neuroinflammation, reduced AChE level, and reduced number of survived neurons in the cortex as indicated from the decreased Bcl2 level and the histological examination.

Cross-talk between down-regulation of steroidogenic genes expression and oxidative and apoptotic biomarkers in testes induced by administration of tramadol and boldenone and their combination in male albino rats.

Objectives: The testis is the male reproductive gland or gonad having two vital functions: to produce both sperm and androgens, primarily testosterone. The study aimed to investigate the effect of tramadol and boldenone injected alone or in combination for 2 months in rats on testicular function. Materials and Methods: Group 1, normal control; Group 2, tramadol HCl (TRAM) (20 mg/kg bwt.) (IP); Group 3, boldenone undecylenate (BOLD) (5 mg/kg bwt) (i.m); Group 4, combination of TRAM (20 mg/kg bwt.) and BOLD (5 mg/kg); respectively for 2 months. Results: TRAM and BOLD alone and in combination showed deteriorated testicular functions, lowered serum steroid levels (FSH, LH, and testosterone), elevation in oxidative biomarkers (MDA & NO) and reduction in GSH and SOD, down-regulation of StaR and HSD17B3 as well as histopathological testicular assessment using H&E staining revealing massive degenerative changes in the seminiferous epithelium and vacuolar changes of most of the spermatogenic stages in both TRAM and BOLD groups. PAS stain showed an intensive reaction in the interstitial tissue between the tubules in the TRAM group. Masson trichrome stain showed abundant collagen fiber deposits in the tunica albuginea with congested BV in the TRAM group. Conclusion: The study illuminated the hazard of administration of these drugs for a long period as well as the prominent deleterious effects reported on concurrent use of both drugs.

Phytochemical constituents and protective efficacy of Schefflera arboricola L. leaves extract against thioacetamide-induced hepatic encephalopathy in rats.

CONTEXT: Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome resulting from liver failure. OBJECTIVE: To evaluate the protective effect of Schefflera arboricola L. leaves methanol extract against thioacetamide (TAA) induced HE in rats. MATERIALS AND METHODS: GC/MS, LC-ESI-MS, and the total phenolic and flavonoid contents were determined. The methanol extract was orally administrated (100 and 200 mg/kg body weight) for 21 days. TAA (200 mg/kg body weight) was given intraperitoneally on day 19 and continued for three days. The evaluation was done by measuring alanine aminotransferase (ALT), alkaline phosphatase (ALP), ammonia, reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), toll-like receptor 4 (TLR4), interleukin-1 beta (IL-1ß), interlukin-6 (IL-6), cyclooxygenase 2 (COX2), B cell lymphoma 2 (BCL2), alpha-smooth muscle actin (α-SMA), and the cluster of differentiation 163 (CD163). The histological features of the liver and brain were conducted. RESULTS: Forty-five compounds were identified from the n-hexane fraction, while twenty-nine phenolic compounds were determined from the methanol extract. Pre-treatment with the plant extract returned most of the measurements under investigation to nearly normal. CONCLUSION: Due to its richness with bioactive compounds, Schefflera arboricola L. leaves methanolic extract succeeded to exert anti-fibrotic, anti-inflammatory, and antioxidants properties in TAA-induced HE in rats with more efficacy to its high protective dose.