Browsing by Author "Abdulkareem Adam Olaitan"

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    Activation of angiotensin converting enzyme 2 promotes hippocampal neurogenesis via activation of Wnt/β-catenin signaling in hypertension
    (2024) Tiwari Priya; Mueed Sumbul; Abdulkareem Adam Olaitan; Kashif Hanif
    Hypertension-induced brain renin-angiotensin system (RAS) activation and neuroinflammation are hallmark neuropathological features of neurodegenerative diseases. Previous studies from our lab have shown that inhi bition of ACE/Ang II/AT1R axis (by AT1R blockers or ACE inhibitors) reduced neuroinflammation and accompanied neurodegeneration via up-regulating adult hippocampal neurogenesis. Apart from this conven tional axis, another axis of RAS also exists i.e., ACE2/Ang (1–7)/MasR axis, reported as an anti-hypertensive and anti-inflammatory. However, the role of this axis has not been explored in hypertension-induced glial activation and hippocampal neurogenesis in rat models of hypertension. Hence, in the present study, we examined the effect of ACE2 activator, Diminazene aceturate (DIZE) at 2 different doses of 10 mg/kg (non-antihypertensive) and 15 mg/kg (antihypertensive dose) in renovascular hypertensive rats to explore whether their effect on glial activation, neuroinflammation, and neurogenesis is either influenced by blood-pressure. The results of our study revealed that hypertension induced significant glial activation (astrocyte and microglial), neuroinflammation, and impaired hippocampal neurogenesis. However, ACE2 activation by DIZE, even at the low dose prevented these hypertension-induced changes in the brain. Mechanistically, ACE2 activation inhibited Ang II levels, TRAF6-NFκB mediated inflammatory signaling, NOX4-mediated ROS generation, and mitochondrial dysfunction by upregulating ACE2/Ang (1–7)/MasR signaling. Moreover, DIZE-induced activation of the ACE2/Ang (1–7)/ MasR axis upregulated Wnt/β-catenin signaling, promoting hippocampal neurogenesis during the hypertensive state. Therefore, our study demonstrates that ACE2 activation can effectively prevent glial activation and enhance hippocampal neurogenesis in hypertensive conditions, regardless of its blood pressure-lowering effects.
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    Dexamethasone Promotes the Risk of Cardiovascular Disease in High Fructose-exposed Wistar Rats
    (2022-10-01) Abdulkareem Adam Olaitan; Abe Emmanuel Olusegun; Olatunji Lawrence Aderemi
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    High parasitaemia correlates with malaria episodes and the socioeconomic impact of recurrent malaria infection in high-transmission zone of Nigeria
    (2022) Babamale Abdulkareem Olarewaju; Abdulkareem Adam Olaitan; Yinka Oyewole Jamiu; Kolawole Folasade; Olatundun Babawale Oluwapelumi; Ayodipo Onitayo Faith Ayodipo; Uddin Mohammad Mosleh; Ugbomoiko Uade Samuel
    Background: Recurrent malaria infection is a major phenomenon in a hightransmission zone with deplorable health and socioeconomic consequences on individuals and the public. However, the association between parasitaemia, repeated episodes of the infection, and its socioeconomic impact is less studied. Therefore, this study aimed at bridg ing this research gap by conducting an epidemiological survey in selected malaria-endemic settings of Kwara state, Nigeria. Results: High prevalence and intensity of infection were observed, 56.6% of 572 study participants were infected with average parasitaemia of 3022.25 ± 1001.51 per µl of blood and the majority of heavy infection was due to Plasmodium falciparum. The heavily asymptomatic infected participants were among the younger age group par ticularly ≤ 20 years, and infection decreases with increasing age. Parasitaemia and the number of episodes of malaria attacks were positively correlated (R2 = 0.2388, p < 0.0001). Highrecurrent malaria was associated with male (p = 0.001), younger age (p = 0.0012), low-income status (p = 0.0004), bush around habitation (0.0014), and unavoidability of preventive strategies and treatment (p < 0.0001) of malaria. Our study further revealed socioeconomic factors as cause and/or consequence of recurrent malaria infection. Low income individuals (aOR 1.948 95%CI 0.945–2.512) and illiterates (aOR 1.920 95%CI 1.470–2.149), those living close to bush (aOR 2.501 95%CI 2.033–3.714) and dumpsite (aOR 2.718 95%CI 1.661–3.118) are at least twice likely to have recurrent infection. The socioeconomic consequence of recurrent malaria episodes includes reduced economic activities, personal savings, and change of lifestyle in adults, while infected children suffered declined academic performance and sports activities. Conclusions: This study underscores high malaria intensity as a prevalent health problem in our study location and demonstrates a positive correlation between malaria episodes and parasitaemia which can be explored in the clinic for the screening of suitable antimalarial drugs that cure beyond a single infection. Our finding also advocates for mass distribution of insecticide-treated nets, provision of socio-infrastructural amenities such as medical centers, good drainage system and highly subsidized malaria treatment in endemic endemic rural communities
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    Inhibition of poly (ADP-ribose) Polymerase-1 (PARP-1) improves endothelial function in pulmonary hypertension
    (2023) Shafiq Mohammad; Lone Zahid Rasool; Abdulkareem Adam Olaitan; Kaura Gurpreet; Sai Navya; Singh Himalaya; Jagavelu Kumaravelu; Kashif Hanif
    Endothelial dysfunction is critical in the pulmonary vasculature during pulmonary hypertension (PH). Moreover, in PH, increased inflammation and oxidative/nitrosative stress cause DNA damage, activating poly (ADP-ribose) polymerase-1 (PARP-1). Meloche et al. (2014) and our previous research have shown that inhibiting PARP-1 is protective in PH and associated RV hypertrophy. However, the role of PARP-1 in pulmonary arterial endothelial dysfunction has not been explored completely. Therefore, the current study aims to investigate the involvement of PARP-1 in endothelial dysfunction associated with PH. Hypoxia (1% O2) was used to induce a PH-like phenotype in human pulmonary artery endothelial cells (HPAECs), and PARP-1 inhibition was achieved via siRNA (60 nM). For the in vivo study, male Sprague Dawley rats were administered monocrotaline (MCT; 60 mg/ kg, SC, once) to induce PH, and 1, 5-isoquinolinediol (ISO; 3 mg/kg) was administered daily intraperitoneally to inhibit PARP-1. PARP-1 inhibition decreased proliferation and inflammation, as well as improved mitochondrial dysfunction in hypoxic HPAECs. Furthermore, PARP-1 inhibition also promoted apoptosis by increasing DNA damage in hypoxic HPAECs. In addition, inhibition of PARP-1 reduced cell migration, VEGF expression, and tubule formation in hypoxic HPAECs. In in vivo studies, PARP-1 inhibition by ISO significantly decreased the RVP and RVH as well as improved endothelial function by increasing the pulmonary vascular reactivity and expression of p-eNOS in MCT-treated rats.
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    Letrozole ameliorates fructose-induced hyperlipidaemia and uric acid accumulation in male Wistar rats
    (2023) Abdulkareem Adam Olaitan; Abe Emmanuel Olusegun; Ala Adeola Adefoluke; Olatunji Lawrence Aderemi
    Introduction: High fructose consumption is commonly associated with increased risk of cardiovascular disease (CVD). However, cardiovascular effects of aromatase inhibitors remain unresolved, although they are effective in the treatment of breast cancer. Thus, this study investigated the effect of letrozole on CVD indicators in Wistar rats exposed to high fructose intake. Methods: Twenty male rats were randomly placed in four groups (n=5/group): control (distilled water), fructose (10% fructose in drinking water), letrozole (1mg/kg) and fructose+ letrozole. After 21-day exposure, fasting blood glucose was taken and the rats were sacrificed, while blood and heart were collected and prepared for biochemical analyses. Results: Our data showed that 10% fructose induced hyperglycaemia and lipid peroxidation. It reduced serum high-density lipoprotein cholesterol, elevated serum total cholesterol (TC), triglycerides and free fatty acid but did not alter serum low-density lipoprotein cholesterol significantly, when compared with the control. Furthermore, high fructose-intake increased serum or cardiac adenosine deaminase (ADA), xanthine oxidase and uric acid. Our findings revealed that letrozole, when taken with 10% fructose, attenuated all the observed fructose induced alterations. However, when administered alone, letrozole elevated serum TC as well as cardiac malondialdehyde and ADA. Conclusion: This study showed that high fructose-intake promoted the risk of CVDs in rats, while administration of letrozole attenuated fructose effects. Hence, letrozole may serve as a potential adjuvant therapy for attenuating CVD risk. However, further pre-clinical and clinical f indings are necessary to thoroughly investigate the cardiometabolic effects of letrozole.
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    LETROZOLE ATTENUATES CARDIOMETABOLIC RISK IN PLASMODIUM BERGHEI-INFECTED MICE
    (2023) Abdulkareem Adam Olaitan; Babamale Abdulkareem Olarewaju; Jesutomisin Caleb Omisope; Oluwabunmi Badmos-king A; Ibiwumi Dare B; Olatunji Lawrence Aderemi; Ugbomoiko Uade Samuel
    Malaria is associated with cardiometabolic disorders, promoting the risk of cardiovascular disease (CVD). We recently demonstrated letrozole’s cardioprotective effects in fructose-exposed male rats. Hence, in this study, we investigated the effect of a low-dose letrozole against cardiometabolic risk in Plasmodium berghei-infected female mice. Twenty female mice were randomly grouped into four (n=5/group): uninfected, infected, letrozole (0.24 mg/kg, p.o/day, without infection), and infected + letrozole. Weekly percentage parasitaemia was recorded. At the end of the 21-day exposure, blood and liver were collected and processed for biochemical analyses. P. berghei infection decreased serum estradiol level after 21-day infection and increased serum and liver levels of malondialdehyde, very low-density lipoprotein cholesterol, triglycerides, and triglycerides/high-density lipoprotein cholesterol (TG/HDL-c) index. Similarly, P. berghei elevated serum uric acid and hepatic total cholesterol levels. Meanwhile, the administered dose of letrozole did not significantly affect serum estradiol but lowered lipid peroxidation, attenuated lipid alterations, and reduced serum uric acid level. We reveal that P. berghei-infection lowered serum estradiol and promoted cardiometabolic risk in female mice, while letrozole lowered parasitaemia and mitigated the associated cardiometabolic risk. Thus, this study is suggestive of letrozole’s potential as an adjuvant therapy for improved management of malaria-induced cardiometabolic complications. Further study is recommended to investigate the anti-malaria potency of letrozole, independent of gender.
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    LETROZOLE SUPPRESSES HEPATIC OXIDATIVE STRESS AND AMELIORATES LIPID ACCUMULATION IN FRUCTOSE-EXPOSED WISTER RATS
    (2022-05-08) Abdulkareem Adam Olaitan; Abe Emmanuel Olusegun; Omilana Oluwafemi Ololade; Olatunji Lawrence Aderemi
    An increase in sugar intake, especially fructose or fructose-containing sweeteners, poses a serious public health challenge globally. Unlike glucose, fructose metabolism results in generation of oxidative stress, which promotes hepatic lipid accumulation and consequently increases the risk of non-alcoholic fatty liver disease (NAFLD). Chronic administration of letrozole has been previously reported to decrease lipid peroxidation and increase antioxidants but its effect on fructose-induced lipid accumulation has not been investigated. Thus, the present study sought to investigate the ameliorative effect of letrozole on hepatic oxidative stress and lipid accumulation in high fructose-taking Wister rats. After 3-week of exposure, our results reveal that fructose intake increased hepatic total cholesterol (p< 0.01), triglycerides (p< 0.001) and free fatty acid (p< 0.001). Similarly, fructose increased hepatic malondialdehyde (MDA) (p< 0.001 vs. control) and decreased catalase and superoxide dismutase activities (p< 0.001 and p < 0.05 vs. control, respectively). Furthermore, our data show that high fructose intake elevated levels of uric acid and xanthine oxidase activity in the liver (p< 0.001 vs. control). However, letrozole treatment attenuated the hepatic lipid accumulation, reduced MDA level, and suppressed uric acid biosynthesis in high fructose-taking rats. Conclusively, this study has demonstrated that high fructose intake induces hepatic uric acid synthesis, generating oxidative stress and promoting hepatic lipid accumulation in male Wister rats, while administration of letrozole attenuates the fructose effects. Our findings, therefore, suggest the efficacy of letrozole in attenuating hepatic lipid accumulation, hence, lowering the risk of NAFLD associated with excessive fructose intake.