Browsing by Author "Badmus, Olufunto"

Now showing 1 - 6 of 6
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    Acetate causes renoprotection like androgen and mineralocorticoid receptors blockade in testosterone-exposed pregnant rats
    (Springer, 2021-01-21) Usman, Taofeek; Adeyanju, Oluwaseun; Areola, Emmanuel; Badmus, Olufunto; Oyeyipo, Ibukun; Olaniyi Kehinde; Oyabambi, Adewumi; Olatunji, Lawrence
    The kidney plays a critical role in human health and deviation from its normal function can lead to severe morbidity and mortality. Exposure to excess testosterone in women has been linked to several disorders, including kidney disorder and act ing undoubtedly through androgen receptor (AR), whereas the involvement of mineralocorticoid receptor (MR) is unclear. Likewise, the renal efect of sodium acetate (SAc) during late gestational exposure to testosterone is not well known. We hypothesized that SAc or MR blockade would protect the kidney of testosterone-exposed pregnant rats against glutathione and adenosine depletion. Twenty-fve pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/ kg) singly or in combination with SAc (200 mg/kg; p.o.), androgen receptor (AR) blocker, futamide (Flu; 7.5 mg/kg; p.o.) or (MR) blocker, eplerenone (Eple; 0.5 mg/kg) between gestational days 14 and 19. Glutathione, adenosine and nitric oxide were decreased while uric acid (UA), xanthine oxidase (XO), malondialdehyde (MDA), lactate dehydrogenase activity and free fatty acids were increased in the kidneys of gestational rats exposed to testosterone. Also, plasma urea and creatinine were elevated. SAc and Eple reversed tested testosterone-induced efects in gestational rats. The exposure to testosterone impairs renal antioxidant defense via AR and MR during late gestation in pregnant rats. The study also provides evidence that sodium acetate protects the kidneys of gestational testosterone-exposed rats against defective antioxidant defense in like manner as MR or AR antagonist.
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    Endoglin inhibition by sodium acetate and flutamide ameliorates cardiac defective G6PD-dependent antioxidant defense in gestational testosterone exposed rats
    (Elsevier, 2018-08-25) Olatunji, Lawrence Aderemi; Areola, Emmanuel Damilare; Badmus, Olufunto
    Gestational androgen excess has been implicated in the development of cardiac dysfunction with poor me chanistic delineation. The role of sodium acetate on cardiac uric acid (UA) production and glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defense in pregnancy is not known. The study therefore sought to test the hypothesis that rats exposed to elevated testosterone in late pregnancy would have increased cardiac UA production and defective G6PD-dependent antioxidant defense. We also hypothesized that sodium acetate (SAc) or androgen receptor blocker, flutamide (Flu) would ameliorate these effects through endoglin inhibition. Twenty-four pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or in combination with SAc (200 mg/kg; po) or Flu (7.5 mg/kg; po) in the late gestation between gestational day 14 and 19. The results showed that in the late gestation, testosterone exposure led to increased plasma and cardiac endoglin. In the heart of rats exposed to gestational testosterone there were elevated lactate dehydrogenase, adenosine deaminase, xanthine oxidase, uric acid (UA), cardiac injury markers and decreased G6PD-dependent antioxidant defense. However, either SAc or Flu comparably ameliorated these testosterone-induced effects. The data from the present study revealed that testosterone exposure in the late gestation causes elevated cardiac Eng that is accompanied by increased UA production and defective G6PD-dependent anti-oxidant defenses. Besides, the findings also suggest that the inhibitory effect of SAc or Flu on endoglin attenuates UA production and enhances the G6PD-dependent anti-oxidant barrier, thereby implying that endoglin may be a potentially novel therapeutic intervention for cardiac dysfunction particularly in pregnancy
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    Sodium acetate and androgen receptor blockade improve gestational androgen excess-induced deteriorated glucose homeostasis and antioxidant defenses in rats roles of adenosine deaminase and xanthine oxidase activities
    (Wolters Kluwer Health, 2018-10) Areola, Emmanuel; Badmus, Olufunto; Usman, Taofeek; Olatunji, Lawrence Aderemi
    Objectives: Nutritional challenges and androgen excess have been implicated in the development of gestational diabetes and poor fetal outcome, but the mechanisms are not well delineated. The effects of short chain fatty acid (SCFA) on glucose dysmetabolism and poor fetal outcome induced by gestational androgen excess is also not known. We tested the hypothesis that blockade of androgen receptor (AR) and suppression of late gestational androgen excess prevents glucose dysmetabolism and poor fetal outcome through suppression of adenosine deaminase (ADA)/xanthine oxidase (XO) pathway. Methods: Twenty-four pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or in combination with SCFA (sodium acetate; 200 mg/kg; po) or AR blocker (flutamide; 7.5 mg/kg; po) between gestational days 14 and 19. Results: The results showed that late gestational androgen excess led to glucose deregulation, poor fetal outcome, increased plasma and hepatic free fatty acid and lactate dehydrogenase (LDH), liver function marker enzymes, malondialdehyde (MDA), uric acid (UA), ADA and XO activities. Conversely, gestational androgen excess resulted in reduced body weight gain, visceral adiposity, plasma and hepatic anti-oxidant defenses (glutathione peroxidase, reduced glutathione/glutathione disulphide ratio, glucose-6-phosphate dehydrogenase, adenosine and nitric oxide). However, all these effects were ameliorated by either sodium acetate or flutamide treatment. Conclusion: The study demonstrates that suppression of testosterone by SCFA or AR blockade protects against glucose deregulation and poor fetal outcome by improvement of anti-oxidant defenses through suppression of ADA/XO pathway. Hence, utility of SCFA should be encouraged for prevention of glucose dysmetabolism and poor fetal outcome.
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    Sodium acetate and androgen receptor blockade improve gestational androgen excess-induced deteriorated glucose homeostasis and antioxidant defenses in rats: Roles of adenosine deaminase and xanthine oxidase activities
    (Elsevier, 2018-08-29) Usman, Taofeek Oluwamayowa; Areola, Emmanuel Damilare; Badmus, Olufunto; Kim, InKyeom; Olatunji, Lawrence Aderemi
    Nutritional challenges and androgen excess have been implicated in the development of gestational diabetes and poor fetal outcome, but the mechanisms are not well delineated. The effects of short chain fatty acid (SCFA) on glucose dysmetabolism and poor fetal outcome induced by gestational androgen excess is also not known. We tested the hypothesis that blockade of androgen receptor (AR) and suppression of late gestational androgen excess prevents glucose dysmetabolism and poor fetal outcome through suppression of adenosine deaminase (ADA)/xanthine oxidase (XO) pathway. Twenty-four pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or in combination with SCFA (sodium acetate; 200 mg/kg; po) or AR blocker (flutamide; 7.5 mg/kg; po) between gestational days 14 and 19. The results showed that late gestational androgen excess led to glucose deregulation, poor fetal outcome, increased plasma and hepatic free fatty acid and lactate dehydrogenase, liver function marker enzymes, malondialdehyde, uric acid, ADA and XO activities. Conversely, gestational androgen excess resulted in reduced body weight gain, visceral adiposity, plasma and hepatic anti-oxidant defenses (glutathione peroxidase, reduced glutathione/glutathione disulphide ratio, glucose-6-phosphate dehydrogenase, adenosine and nitric oxide). However, all these effects were ameliorated by either sodium acetate or flutamide treatment. The study demonstrates that suppression of testosterone by SCFA or AR blockade protects against glucose deregulation and poor fetal outcome by improvement of anti-oxidant defenses and replenishment of hepatic oxidative capacity through suppression of ADA/XO pathway. Hence, utility of SCFA should be encouraged for prevention of glucose dysmetabolism and poor fetal outcome.
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    Suppression of Adenosine Deaminase and Xanthine Oxidase Activities by Mineralocorticoid and Glucocorticoid Receptor Blockades Restores Renal Antioxidative Barrier in Oral Contraceptive-Treated Dam
    (Hindawi, 2021-05-18) Badmus, Olufunto; Areola, Emmanuel; Benjamin, Eleojo; Obekpa, Matthew; Adegoke, Tolulope; Elijah, Oluwatobi; Imam, Aminu; Olajide, Olayemi; Olatunji, Lawrence
    Objective. We tested the hypothesis that postpartum combined oral contraceptive (COC) treatment would induce oxidative stress via the adenosine deaminase-xanthine oxidase pathway in the kidney. We also sought to determine whether mineralocorticoid receptor (MR) or glucocorticoid receptor (GR ) blockade would suppress the activities of ADA and xanthine oxidase caused by postpartum COC treatment in the kidney. Methods. Twenty-four Wistar dams were randomly assigned to 4 groups (n = 6/group). Dams received vehicle (po), COC (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel; po), COC with GR blockade (mifepristone; 80.0 mg/kg; po), and COC with MR blockade (spironolactone; 0.25 mg/kg; po) daily between 3rd and 11th week postpartum. Results. Data showed that postpartum COC caused increased plasma creatinine and urea, increased renal triglyceride/high-density lipoprotein ratio, free fatty acid accumulation, alanine aminotransferase, gamma-glutamyltransferase, uric acid, and activities of renal XO and ADA. On the other hand, postpartum COC resulted in decreased plasma albumin, renal glutathione, and Na+ -K+-ATPase activity with no effect on lactate production. However, MR or GR blockade ameliorated the alterations induced by postpartum COC treatment. The present results demonstrate that MR or GR blockade ameliorates postpartum COC-induced increased activities of ADA and xanthine oxidase and restores glutathione-dependent antioxidative defense. Conclusion. These findings implicate the involvements of GR and MR in renal dysfunctions caused by COC in dams via disrupted glutathione antioxidative barrier.
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    Treatment with acetate during late pregnancy protects dams against testosterone-induced renal dysfunction
    (Elsevier, 2021-01-05) Olatunji, Lawrence Aderemi; Areola, Emmanuel Damilare; Usman, Taofeek Oluwamayowa; Badmus, Olufunto; Olaniyi, Kehinde Samuel
    Cardiometabolic diseases are complicated by renal damage. Gestational hyperandrogenism causes gestational metabolic dysfunction that is associated with fetal and maternal tissue derangements as well as post-partum maternal androgen excess. Acetate (Ace) conferred hepatoprotection in pregnant rats exposed to excess testos terone (Tes). The effect of excess androgenic exposure on maternal kidney during and after pregnancy is not clear. Therefore, this study investigated the effect of late gestational and post-gestational testosterone exposure on renal functions and plausible renoprotective role of gestational Ace treatment in dams. Thirty pregnant Wistar rats were grouped (n ¼ 10/group) and treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) with or without acetate (200 mg/kg sodium acetate; p.o) between gestational days 14 and 19. Data were obtained from half of the animals on gestational day 20. Data were also obtained from the other half (dams) after treatment of animals which received Tes with or without prior gestational acetate treatment with post-gestational Tes (sc; 0.5 mg/kg) for the last 6 days of an 8-week postpartum period. Biochemical and statistical analyses were performed with appropriate methods and SPSS statistical software respectively. Late gestational excess Tes led to low placental weight (p ¼ 0.0001, F ¼ 205.7), poor fetal outcomes, creatinine (p ¼ 0.0001, F ¼ 385.4), urea (p ¼ 0.0001, F ¼ 300.9) and renal uric acid (UA) (p ¼ 0.0001, F ¼ 123.2), gamma-glutamyl transferase (GGT) (p ¼ 0.004, F ¼ 26.9), malondialdehyde (p ¼ 0.0001, F ¼ 45.96), and lactate dehydrogenase (LDH) (p ¼ 0.0002, F ¼ 150.7). Postpartum Tes exposure also caused elevated plasma testosterone (p ¼ 0001, F ¼ 22.15), creatinine (p ¼ 0.0002, F ¼ 15.2), urea (p ¼ 0.01, F ¼ 13.8) and renal UA (p ¼ 0.0001, 226.8), adenosine deaminase (p ¼ 0001, F ¼ 544.7), GGT (p ¼ 0.0002, F ¼ 401.4) and LDH (p ¼ 0.01, F ¼ 23.7). However, gestational acetate treatment ameliorated the renal effects of gestational and post-gestational Tes exposure. Taken together, gestational acetate would pre-programme dams against renal dysfunction caused by Tes exposure.