The ameliorative effect of curcumin on hepatic CYP1A1 and CYP1A2 genes dysregulation and hepatorenal damage induced by fenitrothion oral intoxication in male rats.

This research aimed to assess curcumin (CUR) effects on fenitrothion (FNT), a broad-spectrum organophosphate insecticide, -induced hepatorenal damage. Thirty adult male Wistar rats were allocated at random to five equal groups orally administered distilled water containing 1% carboxyl methylcellulose, corn oil (1 mL/rat), CUR (100 mg/kg b.wt.), FNT (5 mg/kg b.wt.), or CUR + FNT. CUR and FNT were dosed three times a week for two months. At the end of this trial, blood and tissue samples (liver and kidney) were subjected to molecular, biochemical, and histopathological assessments. The results revealed that CUR significantly diminished the FNT-induced up-regulation of hepatic CYP1A1 and CYP1A2 transcriptional levels. Moreover, CUR significantly suppressed the increment of the serum levels of hepatic alanine aminotransferase, gamma-glutamyl transferase, and kidney damage indicators (urea and creatinine) in FNT-intoxicated rats. Furthermore, in the hepatic and renal tissues, CUR remarkably restored the FNT-associated depletion of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione S transferase, catalase, and superoxide dismutase). In addition, CUR notably reduced the FNT-induced increment in malondialdehyde content in the hepatic and renal tissues. Besides, the pathological aberrations in liver and kidney tissues resulting from FNT exposure were significantly abolished in FNT + CUR treated rats. Overall, CUR could be an effective ameliorative agent against negative pesticide impacts like FNT.

Early postmortem biochemical, histological, and immunohistochemical alterations in skeletal muscles of rats exposed to boldenone undecylenate: Forensic implication.

This study investigated the biochemical and histopathological alterations along with the immunoexpression pattern of heat shock protein 27 (Hsp27) within 6 h postmortem (PM) in skeletal muscle of boldenone (BOL)-treated rats. Forty-eight male rats were divided into two groups; a control group received sesame oil (0.25 mL/kg bwt), and BOL group received 5 mg/kg bwt BOL. Both treatments were intramuscularly injected once a week for eight weeks. Rats were euthanized by cervical dislocation, and the skeletal muscle specimens were collected at zero-time, 2, 4, and 6 h PM for biochemical and histopathological evaluations. The results revealed that BOL treatment significantly increased pH, MDA, ATP, ADP, glycogen, and hydroxyproline values. Still, it decreased the GPX, GST, and lactic acid levels, and Hsp27 immunoexpression compared to the control group. With increasing postmortem interval (PMI), whether control or BOL-treated, a significant reduction in pH value, markers of muscular antioxidant status, ATP, ADP, glycogen, hydroxyproline levels, as well as Hsp27 immunoexpression but a significant increase in lipid peroxidation and lactic acid content were recorded. Of note, the interaction between BOL treatment and PMI had a significant effect on ATP, ADP, lactic acid, hydroxyproline, GST, MDA, and TAC levels. Conclusively, these findings signify BOL exposure's modifying effect on the energy content, oxidative status, and histological architecture of skeletal muscles in the early PMI that reflected in delaying the onset of rigor mortis. For forensic practitioners, these findings should be highly considered at estimating PMI in athletic, AAS-treated patients, and fattening animals.

Boldenone undecylenate disrupts the immune system and induces autoimmune clinical hypothyroidism in rats: Vitamin C ameliorative effects.

The present study was designed to evaluate the effects of boldenone undecylenate (BL) abuse alone and in combination with vitamin C (VC) on the immune responses and thyroid structure and function in rats. Thirty adult male Wistar rats were randomly divided into five equal groups and were subjected to various treatment regimens for eight weeks as follows: control group, vehicle control group, VC group orally received VC (120 mg/Kg BW/day), BL-treated group intramuscularly injected with BL (5 mg/kg BW, once/week), and BL+VC group received BL and VC. At the end of this experiment, blood and tissue samples (thyroid, thymus, and spleen) were subjected to hematological evaluation, biochemical analysis, histopathological, and immunohistochemical examinations. In comparison to controls, BL significantly increased the levels of serum proinflammatory interleukins (IL-1 ß and IL-6), immunoglobulins (IgG and IgM), and complement 3 but reduced anti-inflammatory interleukin-10, lysosome, and nitric oxide. Besides, altered platelet count and leukogram were evident in BL-injected rats. BL notably disturbed thyroid profile as revealed by a significant increase of thyroid-stimulating hormone and thyroid peroxidase antibody. In contrast, both total and free forms of thyroid hormones (tri-iodothyronine and thyroxine), thyroglobulin, and thyroid peroxidase, were significantly decreased. Moreover, BL caused histopathological changes in the thyroid, thymus, and spleen tissues.CD4+ immuno-expression was reduced, but CD8+ immunolabelling was increased in both spleen and thymus. The daily dosing of VC to BL-exposed rats significantly corrected most of the deviations in immune parameters. It restored most of the thyroid architecture and function, revealing a significant protective effect of this vitamin. This experimental study demonstrates that BL abusing disrupts the immune system by different mechanisms and addresses BL, for the first time, as an autoimmune clinical hypothyroidism inducer drug. Additionally, VC is helpful in the management of BL abuse.

Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role.

Boldenone Undecylenate (BLD) is a synthetic derivative of testosterone and a widely used anabolic androgenic steroid. The health risk of BLD use as a pharmaceutical or dietary supplement is still underestimated and under-reported. Vitamin C (VC) has been recognized as an antioxidant with prominent hepatorenal protective effects. This study investigated the possible preventive activity of VC against BLD-induced hepatorenal damage. Forty adult male Wistar rats were classified into five groups: control, vehicle control, VC (orally given 120 mg/kg b. wt./day), BLD (intramuscularly injected 5 mg/kg b. wt./week), and BLD + VC-treated groups. The experiment continued for eight weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Serum contents of total protein (TP), albumin (ALB), globulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C) were also assayed. Urea, creatinine, and uric acid levels were determined together with sodium and potassium electrolytes measuring. Moreover, oxidative stress indicators including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GSR) as well as malondialdehyde (MDA) levels were measured in both hepatic and renal tissues. Corresponding histological examination of renal and hepatic tissues was conducted. Besides, immunohistochemical evaluations for androgen receptors protein (AR) and heat shock protein 90 (Hsp 90) expressions were performed. BLD caused significant rises in serum ALT, AST, TP, ALB, TC, TG, LDL-C, VLDL-C, urea, creatinine, uric acid, potassium, and MDA levels. Further, BLD-injected rats showed significant declines in the serum levels of HDL-C, sodium, GSH, GPx, GST, and GSR. Besides, distinct histopathological perturbations were detected in renal and hepatic tissues of BLD-injected rats. AR and Hsp 90 immunoexpression were increased in hepatic and renal tissues. In contrast, VC significantly reversed the BLD-induced hepatorenal damage in co-treated rats but not ameliorated AR protein overexpression. VC could be an efficient preventive supplement for mitigating BLD-induced hepatorenal damage, possibly via controlling oxidative stress events.

The Modulatory Role of Vitamin C in Boldenone Undecylenate Induced Testicular Oxidative Damage and Androgen Receptor Dysregulation in Adult Male Rats.

BACKGROUND: This study explored the effect of vitamin C (Vit-C) administration on the reproductive function of adult male Wistar rats injected with boldenone undecylenate (BOL). METHODS: Rats were randomly assigned into control, vehicle control, Vit-C (120 mg/kg b.wt./day, orally), BOL (received 5 mg/kg b.wt./week, IM) and BOL+Vit-C-treated groups. After eight weeks, hormonal assay, semen evaluation, testicular enzymes, and antioxidants biomarkers were assessed. Besides, the histopathological and immunohistochemical investigations of the androgen receptor (AR) expression were performed. RESULTS: The results revealed that serum testosterone, acid phosphatase, sorbitol dehydrogenase, sperm abnormalities, and testicular malondialdehyde were significantly incremented in the BOL-treated group. Testicular weight, sperm count, and sperm motility together with serum levels of luteinizing hormone, follicle-stimulating hormone, and estradiol, and testicular testosterone, catalase, superoxide dismutase, and reduced glutathione showed a significant decrease following BOL treatment. Besides, the AR immunoreactivity was significantly decreased in testicular tissues. Vit-C co-administration with BOL significantly relieved the BOL-induced sperm abnormalities, reduced sperm motility, testicular enzyme leakage, and oxidative damage. However, Vit-C could rescue neither BOL-induced hormonal disturbances nor AR down-regulation. CONCLUSIONS: The results provide further insight into the mechanisms of BOL-induced reproductive dysfunction and its partial recovery by Vit-C.