Lutein Attenuates Cyclosporin-induced Testicular Impairment in Male Rats through Modulation of Androgenic Hormones and Enzymes

Abstract

Background: Male reproductive toxicity has been linked to cyclosporine, a commonly used immunosuppressive drug for the prevention of organ rejection in patients undergoing renal transplant. The goal of this study was to elucidate how lutein protects male testicles from cyclosporine-induced damage.
 Methods: Thirty adult male Wistar rats were randomly allotted to five groups, each with six animals. Rats in groups 1 and 2 were given saline (2 mL/kg/day p.o) and corn oil (2 mL/day p.o) respectively. Rats in groups 3 and 4 were given lutein (40 mg/kg/day p.o) and cyclosporine (40 mg/kg/p.o./day), while rats in group 5 were given a combination of cyclosporine (40 mg/kg/day p.o) and lutein (40 mg/kg/day p.o). At the end of the fourth week, sperm indices, serum hormones, testicular steroidogenic enzymes [3 and 17 beta-hydroxysteroid dehydrogenases (3?-HSD and 17?-HSD)] and enzyme markers of spermatogenesis [lactate dehydrogenase (LDH-X), sorbitol dehydrogenase (SDH), gamma glutamyl transferase (?-GT), acid phosphatase (ACP) and alkaline phosphatase (ALP)] were assayed. The testis of each rat was also investigated for histopathological abnormalities and germ cell count. 
 Results: Lutein attenuated cyclosporine-induced sperm impairment. In rats treated with cyclosporine, lutein reduced LDH-X, SDH, ACP, ?-GT; raised LH, FSH, testosterone, 3ß-HSD, 17ß-HSD, ALP levels, and improved spermatogenesis.
 Conclusion: These results suggest that lutein attenuates cyclosporine-induced testicular impairment through modulation of androgenic hormones and enzymes.

Possible mechanisms involved in the protective effect of lutein against cyclosporine-induced testicular damage in rats

“…Cyclosporine and lutein were individually dissolved in 20 mL of corn oil and orally administered immediately before use. The dosages and methods of corn oil [ 4 ], cyclosporine (40 mg/kg) [ 5 , 14 ] and lutein (40 mg/kg) were determined based on previous dose-response effects and early research [ 5 , 19 ]. However, saline (2 mL/kg, p.o.)…”

“…Cyclosporine is most typically utilized as a potent immunosuppressant in transplantation surgery and the treatment of autoimmune illnesses [ 5 ]. This is based its high inhibitory activity on lymphokine synthesis, differentiation, and signal transduction pathways of cell T-receptors, the fungal peptide [ 5 ].…”

“…Cyclosporine is most typically utilized as a potent immunosuppressant in transplantation surgery and the treatment of autoimmune illnesses [ 5 ]. This is based its high inhibitory activity on lymphokine synthesis, differentiation, and signal transduction pathways of cell T-receptors, the fungal peptide [ 5 ]. But studies have shown that cyclosporine can has toxic side effects, including vascular dysfunction [ 6 ], hepatotoxicity [ 5 ], ovarian damage [ 7 ], testicular injury [ 8 ], spermatozoal toxicity [ 9 , 10 ], cardiotoxicity [ 11 ].…”

“…This is based its high inhibitory activity on lymphokine synthesis, differentiation, and signal transduction pathways of cell T-receptors, the fungal peptide [ 5 ]. But studies have shown that cyclosporine can has toxic side effects, including vascular dysfunction [ 6 ], hepatotoxicity [ 5 ], ovarian damage [ 7 ], testicular injury [ 8 ], spermatozoal toxicity [ 9 , 10 ], cardiotoxicity [ 11 ]. It is widely accepted that oxidative stress contributes to the toxicity of cyclosporine [ 9 ].…”

Arjunolic acid reverses fluoxetine-induced alterations in testicular steroidogenic enzymes and membrane bound ionic pump imbalance through suppression of oxido-inflammatory stress and apoptosis

“…FXT and AA were dissolved separately in 10 mL of saline immediately before use and administered orally. The doses and routes of Saline ( Oyovwi et al ., 2022 ), FXT at 10 mg/kg ( Sakr et al ., 2015 ) and AA at 1.0 and 2.0 mg/kg body weight were selected based on previous dose-response effects and preliminary investigation. More so, saline (10 mL/kg, p.o.)…”