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

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 a...

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Main Authors: Victor Udo Nna, Ainul Bahiyah Abu Bakar, Azlina Ahmad, Chinedum Ogbonnaya Eleazu, Mahaneem Mohamed
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/8/10/465
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author Victor Udo Nna
Ainul Bahiyah Abu Bakar
Azlina Ahmad
Chinedum Ogbonnaya Eleazu
Mahaneem Mohamed
author_facet Victor Udo Nna
Ainul Bahiyah Abu Bakar
Azlina Ahmad
Chinedum Ogbonnaya Eleazu
Mahaneem Mohamed
author_sort Victor Udo Nna
collection DOAJ
description 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 (<i>p</i> &lt; 0.05) testicular mRNA levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, catalase and glutathione peroxidase; increasing (<i>p</i> &lt; 0.05) the activities of antioxidant enzymes; and decreasing (<i>p</i> &lt; 0.05) lipid peroxidation in the testes and epididymis of diabetic rats. Further, MP down-regulated (<i>p</i> &lt; 0.05) testicular mRNA and protein levels of pro-inflammatory mediators (nuclear factor kappa B, inducible nitric oxide synthase, tumour necrosis factor-&#945; and interleukin (IL)-1&#946;), decreased (<i>p</i> &lt; 0.05) the nitric oxide level, and increased (<i>p</i> &lt; 0.05) IL-10 mRNA and protein levels. MP also down-regulated (<i>p</i> &lt; 0.05) Bax/Bcl-2, p53, casapase-8, caspase-9 and caspase-3 genes, and increased (<i>p</i> &lt; 0.05) testicular germ cell proliferation. MP&#8217;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.
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spelling doaj.art-bcf02c1ba2ec49388d12d76acc8a65d12023-09-03T03:03:11ZengMDPI AGAntioxidants2076-39212019-10-0181046510.3390/antiox8100465antiox8100465Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and MetforminVictor Udo Nna0Ainul Bahiyah Abu Bakar1Azlina Ahmad2Chinedum Ogbonnaya Eleazu3Mahaneem Mohamed4Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaBasic Science and Oral Biology Unit, School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaDepartment of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaOxidative 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 (<i>p</i> &lt; 0.05) testicular mRNA levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, catalase and glutathione peroxidase; increasing (<i>p</i> &lt; 0.05) the activities of antioxidant enzymes; and decreasing (<i>p</i> &lt; 0.05) lipid peroxidation in the testes and epididymis of diabetic rats. Further, MP down-regulated (<i>p</i> &lt; 0.05) testicular mRNA and protein levels of pro-inflammatory mediators (nuclear factor kappa B, inducible nitric oxide synthase, tumour necrosis factor-&#945; and interleukin (IL)-1&#946;), decreased (<i>p</i> &lt; 0.05) the nitric oxide level, and increased (<i>p</i> &lt; 0.05) IL-10 mRNA and protein levels. MP also down-regulated (<i>p</i> &lt; 0.05) Bax/Bcl-2, p53, casapase-8, caspase-9 and caspase-3 genes, and increased (<i>p</i> &lt; 0.05) testicular germ cell proliferation. MP&#8217;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.https://www.mdpi.com/2076-3921/8/10/465antioxidantapoptosisdiabetesinflammationmalaysian propolismetformin
spellingShingle Victor Udo Nna
Ainul Bahiyah Abu Bakar
Azlina Ahmad
Chinedum Ogbonnaya Eleazu
Mahaneem Mohamed
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
antioxidant
apoptosis
diabetes
inflammation
malaysian propolis
metformin
title Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin
title_full Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin
title_fullStr Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin
title_full_unstemmed Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin
title_short Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin–Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin
title_sort oxidative stress nf κb mediated inflammation and apoptosis in the testes of streptozotocin induced diabetic rats combined protective effects of malaysian propolis and metformin
topic antioxidant
apoptosis
diabetes
inflammation
malaysian propolis
metformin
url https://www.mdpi.com/2076-3921/8/10/465
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