Aloysius Obinna Ikwuka

ABSTRACT Rauwolfia vomitoria has been observed to ameliorate and prevent cisplatin-induced neural loss due to its antioxidant and anti-inflammatory properties. To investigate the effects of ethanol extract of R. vomitoria (RV) leaf on lipid profile, oxidative stress biomarkers, and the cerebellar histology using cisplatin-induced oxidative stress in Wistar albino rats. Thirty-six (36) rats were randomly shared into four groups (n=9). Group1 (positive control) received drinking water and rats feed. Group 2 (negative control) received cisplatin (5mg/kg body weight) via intraperitoneal (IP) injection. Group 3 received cisplatin (5mg/kg body weight) and 100mg/kg/day (RV). Group 4 received cisplatin (5mg/kg body weight) and 200mg/kg/day (RV). RV was given for 20 days via oral gavage while the single dose of cisplatin was given intraperitoneally on the first day. On day 21, lipid profile was analyzed, oxidative stress biomarkers activities were determined, and the cerebellum was prepared using Haematoxylin and Eosin (H&E) and Cresyl Violet (CV) staining techniques. Cisplatin elevated total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density Cisplatin is a platinum-based chemotherapy drug used to treat various types of cancers. lipoprotein (LDL) (p>0.05). The TC, HDL, and LDL in the RV-treated groups reduced slightly (p>0.05), while TG was further elevated (p>0.05). The cisplatin group had an insignificant rise (p>0.05) in lipid peroxidation malondialdehyde, glutathione, catalase, and superoxide dismutase. RV further elevated these values. Cisplatin distorted the cerebellar cortex histology by causing altered Purkinje cell bodies, infiltration of the pyknotic Purkinje cells into the granular layer, fatty changes and vacuolation. The cerebellar histology of rats in groups 3 and 4 showed considerable improvement. The administration of ethanol extract of Rauwolfia vomitoria significantly suppressed oxidative stress, increased antioxidative capacity, ameliorated the histological alterations of the cerebellum, and demonstrated neuroprotective ability against cisplatin-induced neurotoxicity. Keywords: Rauwolfia vomitoria, cisplatin, oxidative stress, lipid profile, cerebellar histology, neurotoxicity

ABSTRACT Asymptomatic hyperuricemia is believed to be more severe and more common in patients with dual metabolic syndrome diseases (essential hypertensive disease (EHD) and type 2 diabetes mellitus (T2DM)) and comparatively less severe and less common in patients with either of these dual metabolic syndrome diseases. To determine the heterogeneity of renal pathogenicity on the background of asymptomatic hyperuricemia in the clinical course of EHD combined with T2DM using correlations between uric acid levels in the blood, systolic blood pressure levels, glycated hemoglobin, dyslipidemia, inflammatory processes, kidney damage, etc. The research included 105 patients (50 males and 55 females), aged 41-70 years, average age being (54.2±4.0) years. Patients were divided into 3 groups: Group I (GI) consisted of 25 patients with treatment-compensated EHD, 1-2 degree, stage II; Group ІІ (GII) was made up of 25 patients with subcompensated T2DM (glycated hemoglobin (HbA1C) - from 7.0 to 11.0%); Group III (GIII) had 55 patients with EHD, 1-2 degree, stage ІІ combined with subcompensated T2DM. Control group consisted of 15 practically healthy volunteers, 10 (66.7%) females and 5 (33.3%) males, aged (54.6±4.2) years. Groups were randomized according to age, sex, BMI, duration of EHD and T2DM. In addition to general clinical examination conducted; blood levels of uric acid (UA), lipids, tumour necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP) were determined. Urine levels of neutrophil gelatinase-associated lipocalin (NGAL) was also determined using immuno-fermentation methods. Asymptomatic hyperuricemia characterized by an increase in blood uric acid level of more than 410 μmol/l was observed in 34.6% of GI patients, in 21.8% of GII patients and most commonly in 55.7% of GIII patients with EHD combined with T2DM. Correlations between blood uric acid level with albuminuria was found (r=+0.42; p<0.05); with decrease in GFR (r=-0.51; p<0.05); with increase in NGAL level in urine (r=+0.56; p<0.05), which indicate an adverse effect of asymptomatic hyperuricemia on the functional state of the kidneys in patients with EHD and concomitant T2DM. Positive correlative relationships exist between asymptomatic hyperuricemia, increased albuminuria and a decrease in GFR, dyslipidemia, SBP, HbA1C, inflammatory processes and kidney damage, which indicate the heterogeneity of renal pathogenicity in patients with EHD combined with T2DM and a higher risk of cardiovascular disease in such patients. Keywords: Heterogeneity, renal pathogenicity, asymptomatic hyperuricemia, metabolic syndrome diseases, essential hypertensive disease, type 2 diabetes mellitus