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

Abstract

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.

Experimental studies on androgen administration in animal models: current and future perspectives

“…Moreover, on the basis of their results after treatment with androgens at a high dosage, FSH, LH, and testosterone hormone levels statistically decreased, whereas prolactin and estrogen hormones increased. Behairy et al [12 ▪ ,13 ▪ ], in two different studies, demonstrated several parameters (such as serum testosterone, acid phosphatase, sorbitol dehydrogenase, sperm abnormalities and testicular malondialdehyde) were significantly increased in the androgen-treated group. The same group demonstrated that the vitamin C co-administration may attenuate the adverse effects of androgens.…”

Anabolic Steroids in Fattening Food-Producing Animals—A Review

“…Boldenone, a 1(2)-dehydrogenated analogue of testosterone, differs chemically from testosterone by a double bond between C1 and C2. It is characterized by high anabolic and low androgenic activity and due to its effects muscles grow slower but is of better quality than most testosterone derivatives [ 54 , 55 , 56 ]. It is approved as a veterinary drug in many countries, especially for the treatment of horses, calves, and lambs [ 57 , 58 ].…”

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

“…Despite being banned in humans, boldenone is still available illegally and heavily used by athletes and body builders and for fitness purposes in non-athletics [ 5 ]. Several health disorders have been associated with boldenone misuse like renal damage [ 6 ], cardiovascular disorders [ 7 ], liver dysfunction [ 8 ], and testicular problems [ 9 ] These actions were attributed to the adverse effects of boldenone on the antioxidant mechanisms of these organs [ 7 ]. In addition, a wide range of behavioral and neurochemical alterations have been reported in the nervous system after AAS consumption [ 10 ].…”