Brain antioxidants and hippocampal microanatomical alterations following the administration of Efavirenz/Lamivudine/Tenofovir disoproxil fumarate and Lamivudine/Nevirapine/Zidovudine in adult male Wistar rats.

Highly active antiretroviral therapies (HAARTs) are used for the management of human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS). The present study was designed to characterize the neurotoxicity profile of two popular HAARTs on the brains' antioxidants and hippocampal microanatomical alterations in an in vivo model. Fifteen adults male Wistar rats, were assigned to three groups (n = 5); group I the normal control (NC) received distilled water (5 mL/kg b.wt), groups II administered with oral therapeutic doses of Efavirenz/ Lamivudine/ Tenofovir disproxil fumerate (TLE 17.14 mg/kg b.wt), and group III with Lamivudine/ Nevirapine/ Zidovudine (LNZ 9.28 mg/kg b.wt), respectively which were available for use in University of Uyo Teaching Hospital Nigeria at the time of this experiment. After a 30-day administration, biochemical parameters (catalase, superoxide dismutase, reduced glutathione, glutathione S-transferase, malondialdehyde, glutathione peroxidase, vitamins A, C and E) were determined via serum from blood of ketamine (100 mg/kg, i.p) anesthetized rats. Brains were carefully removed and post-fixed for tissue processing employing hematoxylin and eosin (H&E), cresyl fast violet (CFV) stains, and glial fibrillary acidic protein (GFAP) antibody expression. Results revealed significantly (p < 0.05) decreased antioxidant concentrations and increase in oxidative markers in HAART-administered groups. Normal histoarchitecture was shown in NC, but TLE-administered group demonstrated some neuronal atrophy, and degeneration of pyramidal neurons, with milder distortions in LNZ. TLE-administered group demonstrated intense Nissl substances with chromatolysis compared to LNZ and NC, while GFAP was strongly expressed in TLE-administered group compared to LNZ. In conclusion, TLE is more neurotoxic compared with LNZ.

Carica papaya attenuates testicular histomorphological and hormonal alterations following alcohol-induced gonado toxicity in male rats.

Chronic alcohol consumption has been implicated in male infertility, whereas Carica papaya (CP) ripe fruit possesses antioxidant activity. This study investigated histomorphological and hormonal effects of ripened CP in alcohol experimental model. Thirty Wistar rats were divided into six groups of five animals each as follows; groups 1, 2 and 3 received distilled water 2 ml, 40% ethanol 5 ml, and 40% ethanol 5 ml + 50 mg Clomiphene citrate/kg body weight, respectively, while groups 4, 5 and 6 received 40% ethanol 5 ml + CP 500, 1000 and 1500 mg/kg body weight, respectively. Sperm counts and motility were significantly decreased (p < 0.05) in group 2 compared to group 1. Testosterone significantly increased (p < 0.05) in CP-treated groups, and luteinizing hormone was significantly reduced (p < 0.05) compared to the control. Group 2 showed spermatogenic cell distortions which were ameliorated in the CP-treated groups. CP exerted testicular protective potential against ethanol-induced testicular toxicity plausibly via its antioxidant mechanism.

Investigating the Comparative Effects of Six Artemisinin-based Combination Therapies on Plasmodium-induced Hepatorenal Toxicity.

BACKGROUND: Too many artemisinin-based combination therapies (ACTs) are available, thus creating a dilemma on the most preferred for the treatment of malaria. AIM: We compared the effect of six ACTs in mitigating Plasmodium-induced hepatorenal toxicity in experimental malaria. MATERIALS AND METHODS: Forty adult male Swiss mice allotted into eight groups: Group 1 (normal control [NC] uninfected and untreated), Group 2 (parasitized nontreated - [PNT]), and Groups 3-8 received Plasmodium berghei inoculum. After 72 h, the initial parasitemia was established. Groups 3-8 were administered oral therapeutic doses of artesunate-amodiaquine (AA), artesunate-mefloquine (AM), artesunate-sulfadoxine-pyrimethamine (ASP), artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL) per kg bodyweight, respectively, as standard regimen, and final parasitemia determined. Animals were euthanized via chloroform inhalation and blood collected for hepatorenal analysis. Liver and kidney were dissected out for histology. RESULTS: Parasitemia was significantly (P < 0.05) decreased in tests compared to PNT, except in ASP group. Liver enzymes were significantly (P < 0.05) increased in PNT compared to tests and NC. Hyperplastic cells and portal tract inflammation were prominent in ASP group, but mild to moderate in other treated groups. Urea-creatinine were significantly (P < 0.05) increased in PNT compared to treated groups. The Na+ and Cl- were significantly (P < 0.05) reduced in PNT, with significantly (P < 0.05) increased K+ compared to NC and treated groups. Glomerulonephritis and glomerulus splitting was observed in PNT, while moderate distortions were observed in treated groups. The AA and AM groups had good kidney histoarchitecture. CONCLUSION: Parasitemia decreased in all the treatment groups except in PNT and ASP groups which had severe hepatorenal distortions. Hepatorenal histoarchitecture were mildly distorted in the AA, AM and AL-administered groups with lower hepatorenal indices comparable to NC. The least elevated liver enzymes were in AA and AM. In decreasing order ASP > DP > AL > AP > AM > AA.

Efficacy of six artemisinin-based combination therapies in the attenuation of Plasmodium berghei-induced testicular toxicity in Swiss mice

Many artemisinin-based combination therapies (ACTs) have been approved for malaria treatment, yet reports indicate that some ACTs pose reversible testicular toxicity; however there is no comparative study of these ACTs on the testes in a curative malarial model. We investigated the ameliorative activity of six ACTs on Plasmodium berghei (PB) induced perturbations in testicular antioxidants, serum testosterone levels, sperm motility and the testes microanatomy. Forty male Swiss mice were divided into 8 groups of 5 each: Group 1 normal control (NC), uninfected and untreated, received placebo; group 2 was parasitized non-treated (PNT), while groups 3 - 8 received PB inoculum intraperitoneally. Initial parasitemia was established after 72 hours. Groups 3 - 8 thereafter received oral therapeutic doses of artesunate/amodiaquine (PBAA), artesunate/mefloquine (PBAM), artesunate/sulfadoxine-pyrimethamine (PBASP), artemisinin-piperaquine (PBAP), dihydroartemisinin/piperaquine (PBDP) and artemether/lumefantrine (PBAL) per kg body weight respectively. final parasitemia was performed 24 hours after last treatment, and animals euthanized. Result for parasitemia level was significantly (p < 0.05) declined in ACT-treated groups, except PBASP compared with PNT. Enzymatic antioxidants were significantly (p < 0.0001) altered in ACT-treated groups compared to PNT. Non-enzymatic antioxidants were significantly (p < 0.0001) increased in PBDP compared to NC and PNT. Progressive sperm motility significantly (p < 0.0001) declined in PNT, PBASP, PBAP and PBDP groups compared to NC. Testosterone showed decreasing trend in PBAP compared to PNT, and severe testicular distortions were demonstrated in PNT, PBASP, PBAP and PBDP. This study concludes that therapeutic doses of AA, AM and AL moderately protects against the deleterious effects of Plasmodium berghei-induced testicular toxicity in Swiss mice

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Rauwolfia vomitoria inhibits olfaction and modifies olfactory bulb cells.

The rising cost of orthodox medication has endeared so many to the use of herbs for the management of neurological conditions. Rauwolfia vomitoria (RV) one of such herbs is a rainforest shrub whose parts are used locally in the management of psychiatry and other medical issues. Its usefulness though not in doubt is wrapped with adverse reports as its active constituents depletes brain monoamine and dopamine stores. This motivated this research on the effects of the root bark extract on olfaction and the olfactory bulb of adult Wistar rats. Eighteen adult Wistar rats (220g average) were divided into three groups (n=6); control (placebo), 200mg/kg and 400mg/kg RV root bark extract, respectively. The oral administration lasted for seven days and on day 8, test of olfaction was carried out and the animals immediately anaesthetized with ketamine hydrochloride (i.p.) and perfuse-fixed with 10% neutral buffered formalin. All the brains were processed for histology and immunoreactivity. Results showed loss of body weights and olfaction in the 200mg/kg and 400mg/kg RV groups. There was hypertrophy and atrophy of mitral cells respectively, in the 200mg/kg and 400mg/kg RV groups, while there was hyperplasia of cells in the internal granular and plexiform layers of both groups. There was decreased neuron specific enolase (NSE) and neurofilament (NF) expression in the 200mg/kg RV group, while NF and glial fibrillary acidic protein (GFAP) expression was decreased in the 400mg/kg RV group. However, NSE expression was enhanced in the 400mg/kg group, while GFAP expression was enhanced in the 200mg/kg RV group. These results suggest that these doses of RV affect olfaction and appetite, and stimulate adverse cellular changes in the olfactory bulb.

Effect of preconception gamma irradiation on morphometric assessment of adult female mice and embryo / Efecto de la irradiación gamma preconcepción sobre la evaluación morfométrica de ratones hembras adultas y embriones

The aim was to study the effect of preconception gamma irradiation on the gross morphometry of the adult female mice and its embryo. Twenty-seven mice; 18 females and 9 males: subdivided into 3 groups namely (Control, Non-Irradiation and Radiation) containing 6 females and 3 male mice each in 2:1 ratio. A gamma irradiation dose of 1Gy/min was delivered to each batch of mice exposed by a Cobalt 60, Theratron 780c model, by Atomic Energy of Canada Limited (AECL) at the Radiotherapy department of the University College Hospital, Ibadan. All the animals were mated 1 week post irradiation. Vaginal plugs were confirmed, and the pregnant females were sacrificed on day 14 of gestation by chloroform inhalation. The gross morphology of the female mice and their harvested litters were assessed and statistically analysed. A total of 113 embryos were harvested in all groups; 54 for Control, 50 for Non-Irradiated and 9 for the irradiation group. The gross morphologic assessments of the fetuses were statistically significant at P value < 0.05 for all the 3 groups compared. These findings suggest that a preconception irradiation affects the morphology of the female mice and its progeny.

El objetivo fue estudiar el efecto de la irradiación gamma antes de la concepción sobre la morfometría macroscópica de ratones hembra adultos y los embriones de sus crías. Veinte y siete ratones, 18 hembras y 9 machos, divididos en 3 grupos (control, sin irradiación e irradiado) con 6 hembras y 3 machos cada uno en proporción 2:1. Una dosis de radiación gamma de 1 Gy/min fue aplicada a uno de los ratones expuestos por un equipo Cobalt 60, Theratron modelo 780c, Atomic Energy of Canada Limited (AECL) en el departamento de radioterapia del Hospital University College de Ibadan. Todos los animales se aparearon 1 semana después de la irradiación. Se confirmaron los tapones vaginales, y las hembras preñadas fueron sacrificadas en el día 14 de la gestación por inhalación de cloroformo. La morfología general de los ratones hembras y sus camadas fueron evaluadas y analizadas estadísticamente. Un total de 113 embriones se recolectaron en todos los grupos, 54 del grupo control, 50 del grupo no irradiados y 9 del grupo irradiado. Las evaluaciones morfológicas macroscópicas de los fetos fueron estadísticamente significativas (p<0,05) para los 3 grupos de comparación. Estos hallazgos sugieren que una irradiación previa a la concepción afecta a la morfología de los ratones hembra y su progenie.

Staining characteristics of Lonchocarpus cyanescens leaf extract on the testis of Sprague-Dawley rats.

The use of nonallergic, nontoxic, and eco-friendly natural dyes has become a matter of significant importance due to increased environmental awareness on the need to avoid hazardous synthetic dyes. This study was to determine the staining properties of the dye extract of Lonchocarpus cyanescens on histomorphology of the testis. Freshly cut leaves of L. cyanescens obtained from Akpan Ifia Inan village in Ikono local government area of Akwa Ibom state (latitude 5° 10' 12″ N; longitude 7° 48' 0″ E) were put into a plastic jar and boiling water was poured to cover the leaves. It was covered and left for an hour. The liquid was strained and potassium hydroxide was added to the dye water mixture to reach a pH of 9. A whisk was used to mix air into the liquid, and the mixuture was then allowed to sit until the blue indigo had settled to the bottom of the container. The dye was diluted with 70% ethanol to a concentration of 0.1 g/mL and was used to stain sections of testes. Its potential for use as a counterstain was also investigated. The testes sections were stained in shades of blue. The dye overshadowed the colors of haematoxylin and eosin. Preliminary phytochemical screening of L. cyanescens revealed that it contains alkaloids, saponins, flavonoids, and tannins.