Biochemical and histological alterations of doxorubicin-induced neurotoxicity in rats: Protective role of luteolin.

Doxorubicin (DOX) is a chemotherapeutic drug used in the treatment of various cancer types. DOX toxic side effects include neuronopathy and memory deficits. We investigated the effect of the antioxidant luteolin (LUT: 50 or 100 mg/kg; per os) on DOX (2 mg/kg; intraperitoneal)-induced oxidative stress (OS), inflammation, and apoptosis in the brain of Wistar rats for 14 days. We observed that LUT reduced DOX-mediated increase in OS biomarkers-catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase. LUT increased glutathione and total sulphydryl levels and alleviated DOX-induced increases in the levels of reactive oxygen and nitrogen species, lipid peroxidation, myeloperoxidase, nitric oxide, tumor necrosis factor-α, and interleukin-1ß (IL-1ß). Additionally, LUT suppressed caspase-3 activity, increased anti-inflammatory cytokine-IL-10 level, and reduced pathological lesions in the examined organs of rats cotreated with LUT and DOX. Collectively, cotreatment with LUT lessened DOX-induced neurotoxicity. Supplementation of LUT as a chemopreventive agent might be useful in patients undergoing DOX chemotherapy.

N-acetyl cysteine co-treatment abates perfluorooctanoic acid-induced reproductive toxicity in male rats.

Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140-220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p < .05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. N-acetylcysteine abated (p < .05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.

Kola nut from Cola nitida vent. Schott administered to pregnant rats induces histological alterations in pups' cerebellum.

Kola nut (from Cola nitida) is popular in Nigeria and West Africa and is commonly consumed by pregnant women during the first trimester to alleviate morning sickness and dizziness. There is, however, a dearth of information on its effects on the developing brain. This study, therefore, investigated the potential effects of kola nut on the structure of the developing neonatal and juvenile cerebellum in the rat. Pregnant Wistar rats were administered water (as control) or crude (aqueous) kola nut extract at 400, 600, and 800 mg/kg body weight orally, from pregnancy to day 21 after birth. On postnatal days 1, 7, 14, 21 and 28, the pups were weighed, anaesthetised, sacrificed and perfused with neutral buffered formalin. Their brains were dissected out, weighed and the cerebellum preserved in 10% buffered formalin. Paraffin sections of the cerebellum were stained with haematoxylin and eosin for cerebellar cytoarchitecture, cresyl violet stain for Purkinje cell count, Glial Fibrillary Acidic Protein (GFAP) immunohistochemistry (IHC) for estimation of gliosis, and B-cell lymphoma 2 (Bcl-2) IHC for apoptosis induction. The kola nut-treated rats exhibited initial reduction in body and brain weights, persistent external granular layer, increased molecular layer thickness, and loss of Bergmann glia. Their Purkinje cells showed reduction in density, loss of dendrites and multiple layering, and their white matter showed neurodegeneration (spongiosis) and GFAP and Bcl-2 over-expression, with evidence of reactive astrogliosis. This study, therefore, demonstrates that kola nut, administered repeatedly at certain doses to pregnant dams, could disrupt normal postnatal cerebellar development in their pups. The findings suggest potential deleterious effects of excessive kola nut consumption on human brain and thus warrant further studies to understand the wider implications for human brain development.

The role of Calotropis procera in phenytoin induced toxicity in the postnatal developing cerebellum of Wistar rats - histologicaland gross morphometric studies

The role of methanolic leaf extracts of Calotropis procera in phenytoin-induced toxicity in the postnatal developing cerebellum of Wistar rat was studied.Forty sexually mature female rats, weighing about 160 g of the Wistar strain were randomly divided into five groups of eight animals per group. They were mated and pregnancy confirmed by the presence of a vaginal plug. The animals were fed with a standard diet of rat pellets and water provided ad libitum. The control animals received water, while the test groups received 50 mg/kg of phenytoin, 300 mg/kg, methanolic extracts of Calotropis procera and 200 mg/kg vitamin C orally, both separately and in combination during and after pregnancy. At the end of the experiment, the offspring for days 1, 7, 14, 21, 28 and 50 post-partum, five per group, were weighed and killed. The brains and cerebella were dissected out and weighed and the cerebella processed for histological studies.In the phenytoin-treated animals the results showed a non significant reduction in the body weight of the animals, P>0.05, and a significant reduction in the brain and cerebellar weights, P<0.05, was observed. The administration of extracts of Calotropis procera and vitamin C reversed these changes when compared with the phenytoin-treated group, but not significantly when compared with the control. Histologically, the outer molecular, Purkinje and inner granular layers of the cerebellar cortex were intact, and in all the groups the external granular layer was not seen on day 21 post-partum.In conclusion, supplementation with methanolic extracts of Calotropis procera reduced the rate at which phenytoin induced toxicity in the postnatal developing cerebellum of Wistar rats (AU)

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A Comparison of the Effect of Chlorhexidine, Tap Water and Normal Saline on Healing Wounds / Comparación del Efecto de Clorhexidina, Agua Corriente y Suero Salino en Curación de Heridas

Many researchers have advocated in recent times that antiseptic use in healing wounds should be discouraged. Antiseptics have been found to retard healing of wounds. Innocuous solutions like normal saline and tap water are being considered as better alternatives to antiseptics. Chlorhexidine, a commonly used antiseptic, is known to be less toxic on granulation cells. We decided to compare the effect of chlorhexidine, normal saline and tap water on healing wounds. Three groups of wistar rats had 2 by 2cm full thickness wounds made on their right dorsolateral flanks. The wounds were dressed with either chlorhexidine, normal saline or tap water. Wounds were examined at three-day intervals and measurements of area covered were taken on the first day of study and the ninth day. Wound contraction on the ninth day and number of days for healing to take place in the different groups was taken and statistical analysis using student t-test was done to compare the values. Gross morphology of the wounds was also observed. The result showed an inhibitory effect of chlorhexidine on healing wounds. The wound contraction in the antiseptic group was less than the tap water and saline group on day nine. The average number of days for wound healing to be completed in the antiseptic group was more than the other two. These results were statistically significant when compared with the other two groups. There was no statistical difference in the wound contraction values and rate of healing of the saline and tap water dressed wounds. Grossly, all the wounds dressed with antiseptic also had greenish exudates on their surface by day nine with pale looking granulation tissue, and there was greater mortality in this group.

En la actualidad, diversos investigadores han propagado que el uso de antisépticos en heridas en cicatrización debería, ser abandonado. Se ha encontrado que los antisépticos retardan la cicatrización. Soluciones inocuas, tales como, suero salino y agua corriente, están siendo consideradas como mejores alternativas para efectos antisépticos. La clorhexidina, un antiséptico comúnmente usado, es conocida por ser menos tóxica sobre las células granulares. Basado en lo anterior, comparamos los efectos de la clorhexidina, suero salino y agua corriente en heridas en cicatrización. A tres grupos de ratas Wistar se les infirió heridas de 2 x 2 cm de grosor, en su flanco dorsolateral derecho. La heridas fueron cubiertas (pinceladas) con clorhexidina, solución salina o agua corriente, según el caso. Estas heridas fueronn examinadas cada tres días y las mediciones del área cubierta fueron registradas desde el primero al noveno día. La contracción de la herida al noveno día y el número de días que llevó para cicatrizar se regsitraron en los diversos grupos, analizando los resultados esatadísticamente, usando el test t- student para comparar los valores. La morfología macroscópica también fue observada. Los resultados mostraron un efecto inhibidor de la clorhexidina sobre la cicatrización. La contracción de la herida en el grupo con antiséptico fue menor que en los grupos con suero salino y agua corriente. El promedio de días para cicatrizar, fue mayor en el grupo con antiséptico. Estos resultados fueron estadísticamente significativos al compararlos con los otros dos grupos. No hubo diferencias estadísticamente significativas en los valores de contracción de la herida y rango de cicatrización en el grupo tratado con suero salino normal y en el con agua corriente. Desde el punto de vista macroscópico, las heridas tratadas con el antiséptico también tuvieron un exudado verdoso sobre su superficie al día noveno con un tejido granular pálido y hubo mayor ...