Browsing by Author "Olatunji, Lawrence"

Now showing 1 - 4 of 4
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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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    Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome
    (Elsevier, 2023-06-13) Olaniyi, Kehinde; Areloegbe, Stephanie; Areola, Emmanuel; Sabinari, Isaiah; Fafure, Adedamola; Agbana, Richard; Atuma, Chukwubueze; ul haq Shah, Mohd Zahoor; Ajadi, Isaac; Olatunji, Lawrence
    Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women and it is associated with overt metabolic derangement. Circulating lipids are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9) which blocks low density lipoprotein (LDL) receptors especially in the liver. The liver is highly vulnerable in dyslipidemia as lipid accumulation leads to progression of non-alcoholic fatty liver disease (NAFLD). An array of scientific endeavours hold that low-dose spironolactone (LDS) is beneficial as intervention for PCOS traits, but this claim is yet to be fully elucidated. The aim of this study was to investigate the effect of LDS on dyslipidemia and hepatic inflammation in rats with letrozole (LET)-induced PCOS and to assess the possible involvement of PCSK9 in these effects. Eighteen female Wistar rats were randomly assigned into 3 groups. The control group received vehicle (distilled water; p.o.), LET-treated group received letrozole (1 mg/kg; p.o.), LET+LDS-treated group received LET plus LDS (0.25 mg/kg, p.o.) for 21 days. Exposure to LET increased body and hepatic weights, plasma and hepatic total cholesterol (TC), TC/HDL, LDL, interleukin-6, MDA, PCSK9, ovarian degenerated follicles and hepatic NLRP3 intensity, reduced GSH and normal ovarian follicles. Interest ingly, LDS averted dyslipidemia, NLRP3-dependent hepatic inflammation and ovarian PCOS traits. It is evident herein that LDS ameliorates PCOS traits and combats dyslipidemia and hepatic inflammation in PCOS by a PCSK9-dependent mechanism.
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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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    Suppression of HDAC by sodium acetate rectifies cardiac metabolic disturbance in streptozotocin-nicotinamide-induced diabetic rats
    (Society for Experimental Biology and Medicine, 2020-03-17) Olaniyi, Kehinde; Amusa, Oluwatobi; Areola, Emmanuel; Olatunji, Lawrence
    Diabetes mellitus, particularly type 2 occurs at global epidemic proportions and leads to cardiovascular diseases. Molecular studies suggest the involvement of epigenetic altera tions such as histone code modification in the progression of cardiometabolic disorders. However, short chain fatty acids (SCFAs) are recognized as epigenetic modulators by their histone deacetylase inhibitory property. It is therefore hypothesized that cardiac histone deacetylase activity increases in type II diabetes and SCFA, acetate, would inhibit histone deacetylase with accompanying restoration of glucose dysregulation, cardiac lipid deposi tion, and tissue damage in male Wistar rats. Twenty-four male rats (240–270 g) were allotted into four groups (n ¼ 6 per group) namely: vehicle-treated (p.o.), sodium acetate-treated (200 mg/kg), diabetic, and diabeticþ sodium acetate-treated groups. Diabetes was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of nicotinamide 110 mg/kg. The results showed that diabetic rats had, glucose dysregulation, elevated serum and cardiac triglyc eride, malondialdehyde, alanine aminotransferase, histone deacetylase, serum aspartate transaminase, cardiac low density lipoprotein cholesterol (LDLc), glutathione/glutathione disulphide ratio (GSH/GSSG), reduced serum and cardiac high density lipoprotein cholesterol (HDLc), and serum GSH/GSSG. Histological analysis revealed disrupted cardiac fiber in diabetic rats. However, sodium acetate attenuated glucose dysregulation and improved serum and cardiac GSH/GSSG. Sodium acetate normalized cardiac triglyceride accumulation, malondialdehyde, serum aspartate transaminase levels and prevented cardiac tissue damage in diabetic rats. These effects were associated with suppressed histone deacetylase activity. Therefore, sodium acetate attenuated but failed to normalize glucoregulation. Nevertheless, it ameliorated oxidative stress- and lipid dysmetabolism-driven cardiovascular complications in diabetic rats by the suppression of histone deacetylase activity.