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Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin

1
Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
2
Department of Physiology, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, Calabar P.M.B. 1115, Cross River State, Nigeria
3
Basic Science and Oral Biology Unit, School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
4
Department of Chemistry/Biochemistry/Molecular Biology, Federal University Ndufu Alaike Ikwo, Abakiliki P.M.B. 10, Ebonyi State, Nigeria
5
Unit of Integrative Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(10), 465; https://doi.org/10.3390/antiox8100465
Received: 17 September 2019 / Revised: 5 October 2019 / Accepted: 8 October 2019 / Published: 9 October 2019
Oxidative stress, inflammation and apoptosis are major complications that trigger organ failure in diabetes mellitus (DM), and are proven to adversely affect the male reproductive system. Clinical and experimental studies have demonstrated the promising protective effects of propolis in DM and its associated systemic effects. Herein, we investigated the effect of Malaysian propolis (MP) on testicular oxidative stress, inflammation and apoptosis in diabetic rats. Further, the possibility of a complementary effect of MP with the anti-hyperglycaemic agent, metformin (Met), was studied with the idea of recommending its use in the event that Met alone is unable to contain the negative effects of DM on the male reproductive system in mind. Male Sprague-Dawley rats were either gavaged distilled water (normoglycaemic control and diabetic control groups), MP (diabetic rats on MP), Met (diabetic rats on Met) or MP+Met (diabetic rats on MP+Met), for 4 weeks. MP decreased oxidative stress by up-regulating (p < 0.05) testicular mRNA levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, catalase and glutathione peroxidase; increasing (p < 0.05) the activities of antioxidant enzymes; and decreasing (p < 0.05) lipid peroxidation in the testes and epididymis of diabetic rats. Further, MP down-regulated (p < 0.05) testicular mRNA and protein levels of pro-inflammatory mediators (nuclear factor kappa B, inducible nitric oxide synthase, tumour necrosis factor-α and interleukin (IL)-1β), decreased (p < 0.05) the nitric oxide level, and increased (p < 0.05) IL-10 mRNA and protein levels. MP also down-regulated (p < 0.05) Bax/Bcl-2, p53, casapase-8, caspase-9 and caspase-3 genes, and increased (p < 0.05) testicular germ cell proliferation. MP’s effects were comparable to Met. However, the best results were achieved following co-administration of MP and Met. Therefore, we concluded that administration of the MP+Met combination better attenuates testicular oxidative stress, inflammation and apoptosis in DM, relative to MP or Met monotherapy, and may improve the fertility of males with DM. View Full-Text
Keywords: antioxidant; apoptosis; diabetes; inflammation; Malaysian propolis; metformin antioxidant; apoptosis; diabetes; inflammation; Malaysian propolis; metformin
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Nna, V.U.; Abu Bakar, A.B.; Ahmad, A.; Eleazu, C.O.; Mohamed, M. Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin. Antioxidants 2019, 8, 465.

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