Artemisia judaica L. diminishes diabetes-induced reproductive dysfunction in male rats via activation of Nrf2/HO-1-mediated antioxidant responses

Abdulaziz S Saeedan; Gamal A Soliman; Rehab F Abdel-Rahman; Reham M Abd-Elsalam; Hanan A Ogaly; Ahmed I Foudah; Maged S Abdel-Kader

doi:10.1016/j.sjbs.2020.12.013

Artemisia judaica L. diminishes diabetes-induced reproductive dysfunction in male rats via activation of Nrf2/HO-1-mediated antioxidant responses

Saudi J Biol Sci. 2021 Mar;28(3):1713-1722. doi: 10.1016/j.sjbs.2020.12.013. Epub 2020 Dec 17.

Authors

Abdulaziz S Saeedan¹, Gamal A Soliman^{1

2}, Rehab F Abdel-Rahman³, Reham M Abd-Elsalam⁴, Hanan A Ogaly^{5

6}, Ahmed I Foudah⁷, Maged S Abdel-Kader^{7

8}

Affiliations

¹ Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
² Department of Pharmacology, College of Veterinary Medicine, Cairo University, Egypt.
³ Department of Pharmacology, National Research Centre, Egypt.
⁴ Department of Pathology, College of Veterinary Medicine, Cairo University, Egypt.
⁵ Department of Chemistry, College of Science, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Biochemistry, College of Veterinary Medicine, Cairo University, Egypt.
⁷ Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁸ Department of Pharmacognosy, College of Pharmacy, Alexandria University, Alexandria 21215, Egypt.

Abstract

Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12 weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.

Keywords: AJ, Artemisia judaica L.; Artemisia judaica; CAT, Catalase; DC, Diabetic control; Diabetes; EDTA, Ethylenediamine tetraacetic acid; ELISA, ELISA: Enzyme-linked immunosorbent assay; FBG, Fasting blood glucose; FSH, Follicle stimulating hormone; Fertility; GSH, Reduced glutathione; GSH-Px, Glutathione peroxidase; H&E, Hematoxylin and eosin; HO-1; HO-1, Heme oxygenase-1; HPTLC, High-performance thin layer chromatography; HbA1c, Glycosylated hemoglobin; LH, Luteinizing hormone; LPO, Lipid peroxidation; MDA, Malondialdehyde; NC, Negative control; Nrf2; Nrf2, Nuclear factor erythroid 2-related factor 2; PCNA, Proliferating cell nuclear antigen; ROS, Reactive oxygen species; RT-PCR, Real time polymerase chain reaction; SOD, Superoxide dismutase; STZ, Streptozotocin; TST, Testosterone.