Antidiabetic Botanicals and their Potential Benefits in the Management of Diabetes Mellitus

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Impairment of Hepatic and Renal Functions by 2,5-Hexanedione Is Accompanied by Oxidative Stress in Rats

2,5-Hexanedione (2,5-HD) is the toxic metabolite of n-hexane which is widely used as solvent in numerous industries. The present study elucidated the precise mechanism of 2,5-HD in hepatorenal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were exposed to 0, 0.25, 0.5, and 1% 2,5-HD in drinking water for 21 days. Exposure to 2,5-HD caused liver and kidney atrophy evidenced by significant elevation in serum aminotransferases, alkaline phosphatase, albumin, bilirubin, urea, creatinine, and electrolytes levels compared with control. The marked dose-dependent increase in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was accompanied with significant decrease in high-density lipoprotein (HDL) levels in 2,5-HD-exposed animals when compared with the control. Administration of 2,5-HD significantly diminished glutathione (GSH) level but increased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) concomitantly with marked elevation in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in liver and kidney of the treated groups compared with control. These findings suggest that undue exposure to 2,5-HD at environmentally relevant levels may impair liver and kidney functions through induction of oxidative stress

Atrazine: cytotoxicity, oxidative stress, apoptosis, testicular effects and chemopreventive Interventions

Atrazine (ATZ) is an environmental pollutant that interferes with several aspects of mammalian cellular processes including germ cell development, immunological, reproductive and neurological functions. At the level of human exposure, ATZ reduces sperm count and contribute to infertility in men. ATZ also induces morphological changes similar to apoptosis and initiates mitochondria-dependent cell death in several experimental models. When in vitro experimental models are exposed to ATZ, they are faced with increased levels of reactive oxygen species (ROS), cytotoxicity and decreased growth rate at dosages that may vary with cell types. This results in differing cytotoxic responses that are influenced by the nature of target cells, assay types and concentrations of ATZ. However, oxidative stress could play salient role in the observed cellular and genetic toxicity and apoptosis-like effects which could be abrogated by antioxidant vitamins and flavonoids, including vitamin E, quercetin, kolaviron, myricetin and bioactive extractives with antioxidant effects. This review focuses on the differential responses of cell types to ATZ toxicity, testicular effects of ATZ in both in vitro and in vivo models and chemopreventive strategies, so as to highlight the current state of the art on the toxicological outcomes of ATZ exposure in several experimental model systems

Clinical effects of Garcinia kola in knee osteoarthritis

<p>Abstract</p> <p>Objectives</p> <p>Over the past years, there has been a growing number of knee osteoarthritis (KOA) patients who are not willing to comply with long-term non-steroidal anti-inflammatory drugs (NSAID) treatment and wish to use herbal anti- rheumatic medicine. This study assessed the clinical effects of <it>Garcinia kola </it>(GK) in KOA patients.</p> <p>Patients and methods</p> <p>Prospective randomized, placebo controlled, double blind, clinical trial approved by the institutional medical ethics review board and written informed consent obtained from each patient. All KOA patients presenting at the Obafemi Awolowo University Teaching Hospital complex were recruited into the study. The patients were grouped into four (A = Placebo, B = Naproxen, C = <it>Garcinia kola</it>, D = Celebrex). The drugs and placebo were given twice a day per oral route. Each dose consisted of 200 mg of <it>G. kola</it>, Naproxen (500 mg), Celebrex (200 mg) and Ascorbic acid (100 mg). The primary outcome measure over six weeks study period was the change in mean WOMAC pain visual analogue scales (VAS). Secondary outcome measures included the mean change in joint stiffness and physical function (mobility/walking).</p> <p>Results</p> <p>143 patients were recruited, 84 (58.7%, males – 24, females – 60) satisfied the selection criteria and completed the study. The effect of knee osteoarthritis bilateralism among the subjects was not significant on their outcome (p > 0.05). The change in the mean WOMAC pain VAS after six weeks of <it>G. kola </it>was significantly reduced compared to the placebo (p < 0.001). Multiple comparisons of the mean VAS pain change of <it>G. kola </it>group was not lowered significantly against the naproxen and celebrex groups (p > 0.05). The onset of <it>G. kola </it>symptomatic pain relief was faster than the placebo (p < 0.001). However, it was slower than the active comparators (p > 0.05). The duration of therapeutic effect of <it>Garcinia kola </it>was longer than the placebo (p > 0.001). <it>G. kola </it>period of effect was less than naproxen and celebrex (p < 0.001). <it>G. kola </it>subjects had improved mean change mobility/walking after six weeks better than the control group(p < 0.001). The mean change in mobility of the <it>G. kola </it>group when compared to the active comparators was not significantly better (p < 0.05). The mean change of knee joint stiffness (p < 0.001) and the change of mean WOMAC score (p < 0.001) were improved on <it>Garcinia kola </it>as compared to the placebo. The mid term outcome of eleven <it>Garcinia kola </it>subjects after cessation of use had a mean pain relief period of 17.27 +/- 5.15 days (range: 9–26 days). There was no significant cardiovascular, renal or drug induced adverse reaction to <it>Garcinia kola</it>.</p> <p>Conclusion</p> <p><it>Garcinia kola </it>appeared to have clinically significant analgesic/anti-inflammatory effects in knee osteoarthritis patients. <it>Garcinia kola </it>is a potential osteoarthritis disease activity modifier with good mid term outcome. Further studies are required for standardization of dosages and to determine long-term effects.</p

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease

The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD

From father to son: transgenerational effect of tetracycline on sperm viability

The broad-spectrum antibiotic tetracycline is used in animal production, antimicrobial therapy, and for curing arthropods infected with bacterial endosymbionts such as Wolbachia. Tetracycline inhibits mitochondrial translation, and recent evidence indicates that male reproductive traits may be particularly sensitive to this antibiotic. Here, we report the first multi-generation investigation of tetracycline's effects on ejaculate traits. In a study of the pseudoscorpion, Cordylochernes scorpioides, in which siblings were randomly assigned to control and tetracycline treatments across replicate full-sibling families, tetracycline did not affect body size in either sex, female reproduction or sperm number. However, tetracycline-treated males exhibited significantly reduced sperm viability compared to control males, and transmitted this toxic effect of tetracycline on sperm to their untreated sons but not to their F2 grandsons. These results are consistent with tetracycline-induced epigenetic changes in the male germline, and suggest the need for further investigation of transgenerational effects of tetracycline on male reproductive function

The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact

\ua9 2024 The Authors. Alzheimer\u27s &amp; Dementia published by Wiley Periodicals LLC on behalf of Alzheimer\u27s Association.Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. Highlights: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Lablab Purpureus Seeds Disrupt Hepatic and Renal Antioxidant Status in Male Rats

Nutrition constitutes an essential aspect of health care in both humans and other animals. Despite the numerous studies conducted on Lablab purpureus seeds, there is a paucity of information on its effects on hepatic and renal antioxidant status. The present study investigated the influence of three varieties of Lablab purpureus seeds (Rongai Brown, Rongai White and Highworth Black) on hepatorenal antioxidant status in male Wistar rats. Group I (control) rats were fed with the standard rat chow for 14 days while Groups II, III and IV rats were separately fed with feed containing the Rongai Brown, Rongai White and Highworth Black for 14 days, respectively. Lablab purpureus caused a significant decrease in renal superoxide dismutase (SOD) but increased hepatic SOD activity along with increased catalase, glutathione- S-transferase and glutathione peroxidase activities in both liver and renal tissues when compared with the control. Moreover, there was a significant decrease in the hepatic glutathione (GSH) level with concomitant elevation in hepatic and renal hydrogen peroxide and lipid peroxidation levels in all Lablab purpureus-fed rats. Lablab purpureus-fed rats demonstrated significant elevations in serum marker enzymes, aspartate aminotransferase and alkaline phosphatase along with increases in urea and creatinine levels. Histopathologically, kidney sections revealed normal renal architecture, whereas treatment-related lesions were identified in the liver of Lablab purpureus-fed rats. This study concluded that consumption of raw Lablab purpureus seeds induced hepatorenal toxicity in rats via the induction of oxidative stress

Effects of Xylopia aethiopica (Annonaceae) fruit methanol extract on γ-radiation-induced oxidative stress in brain of adult male Wistar rats

Xylopia aethiopica (XA) (Annonaceae) possesses great nutritional and medicinal values. This study was designed to investigate the effects of XA fruit methanol extract on oxidative stress in brain of rats exposed to whole body γ-radiation (5 Gy). Vitamin C (VC) served as standard antioxidant. Forty-four rats were divided into 4 groups of 11 rats each. One group served as control, two different groups were treated with XA and VC (250 mg/kg), 6 weeks before and 8 weeks after irradiation, and fourth group was only irradiated. Rats were sacrificed 1 and 8 weeks after irradiation. The antioxidant status, viz. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione (GSH) were estimated. Results indicate a significant increase ( p < 0.05) in levels of brain LPO after irradiation. LPO increased by 90% and 151%, after 1 and 8 weeks of irradiation, respectively. Irradiation caused significant ( p < 0.05) decreases in levels of GSH and GST by 61% and 43% after 1 week and, 75% and 73%, respectively, after 8 weeks of exposure. CAT and SOD levels were decreased by 62% and 68%, respectively, after 8 weeks of irradiation. Treatment with XA and VC ameliorated the radiation-induced decreases in antioxidant status of the animals. These suggest that XA could have beneficial effect by inhibiting oxidative damage in brain of exposed rats