DEPARTMENT OF ANATOMY

EFFECTS OF TENOFOVIR DISOPROXIL FUMURATE/LAMIVUDINE/ DOLUTEGRAVIR (TLD) ON THE HISTOMORPHOMETRIC AND REPRODUCTIVE PARAMETERS OF THE OVARY, UTERUS, AND PLACENTA OF ADULT WISTAR RATS

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Human Immunodeficiency Virus (HIV) infection remains one of the leading causes of morbidity and mortality worldwide. Since the beginning of the epidemic, approximately ninety-one million four hundred thousand people have been infected with HIV, and about forty-four million one hundred thousand have died from AIDS-related illnesses. Globally, in 2024, forty million eight hundred thousand people were living with HIV, six hundred thirty thousand people died from AIDS-related illnesses, and one million three hundred thousand people were newly infected with HIV. Tenofovir Disoproxil Fumarate/ Lamivudine/Dolutegravir (TLD) is one of the therapeutic regimens used in the management of HIV infection. This study assessed the effects of TLD on the histomorphometric and reproductive parameters of the ovary, uterus, and placenta of adult Wistar rats. A total of fifty adult female Wistar rats, weighing between 140 g and 194 g, were used for the study. The rats were randomly assigned to control and treated groups, consisting of twenty-five rats, and were further subdivided into five subgroups of five rats each. Both groups received growers mash and distilled water; however, the treated group was administered a daily oral dose of a combination drug consisting of Tenofovir Disoproxil Fumarate (5 mg/kg body weight), Lamivudine (5 mg/kg body weight), and Dolutegravir (0.8 mg/kg body weight) via an orogastric tube. After ninety days of TLD administration, animals with regular four-day estrous cycles were weighed and mated. The animals were categorized into pregestational, gestational, and postnatal groups. The pregestational group was used to evaluate the effects of TLD on antioxidant status, hormonal profile, and histomorphometry of the ovary and uterus. The gestational group was used to assess implantation/resorption, and placenta parameters, while the postnatal group was used to evaluate litter size, litter weight, intrauterine and neonatal death, growth retardation, and congenital anomalies. This study reveals that TLD treatment resulted in a significant decrease in body weight (p < 0.05) but did not significantly affect ovarian, uterine weights and uterine horn length (p > 0.05). Ovarian antioxidant status showed no significant changes; however, the uterus exhibited reduced malondialdehyde (MDA) levels and increased superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. The placenta showed significantly reduced glutathione (GSH) levels. Serum testosterone levels were significantly reduced (p < 0.05). No significant differences were observed in litter number, implantation sites, or number of placenta (p > 0.05). However, litter size and placenta weights were significantly reduced, with evidence of intrauterine growth retardation and low birth weight. Histological findings revealed impaired follicular maturation characterized by atretic follicles, follicular and luteal cysts, narrowing of the endometrial cavity, and thickened endometrium in the treated group. Additionally, dilation, congestion, and vacuolation of the feto-maternal vascular bed were observed. In conclusion, TLD exerted notable adverse effects on reproductive parameters in female Wistar rats, suggesting the need for caution in its use among women of reproductive age
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co-supervisor

EFFECTS OF BILATERAL ORCHIDECTOMY ON HORMONE PROFILE OF MALE WISTAR RATS

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Bilateral orchidectomy is a surgical procedure usually carried out for males with prostate cancer and other diseases affecting both testes. This study was carried out to observe the effect of bilateral orchidectomy on the gonadotropin hormones, (LH, FSH), PRL and the steroid hormones, (Progesterone, Testosterone and Oestrogen). Ten (10) male Wistar rats were used for the experiment. The rats were divided into two experimental groups: 1- control (Co) (n=5), 2 - Treatment group (Tr) (n=5). The rats in the treatment group were bilaterally orchidectomized under chloroform anaesthesia. The rats were sacrificed after 4 weeks. Blood samples were collected from the IVC and assayed for LH, FSH, Prolactin, Progesterone, Testosterone and Oestrogen hormones. The study showed that bilateral orchidectomy increased serum levels of LH and FSH concentrations (3.247±0.152 and
1.177±0.039) which were statistically significant (p<0.05). There was no change in the serum level of Prolactin (p>0.05). However there was statistically significant decrease (p<0.05) in the serum concentrations of Progesterone, Testosterone and Oestrogen. This study showed that bilateral orchidectomy increased serum level of LH and FSH, the two hormones principally required for stimulating Testosterone production and spermatogenesis respectively. The sex steroids, Progesterone, Testosterone and Oestrogen were decreased. Testosterone is needed for spermatogenesis and in conjunction, FSH results in spermiation. The decrease in testosterone therefore may lead to infertility in the castrated rats.
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co-supervisor

EFFECT OF CARBON TETRACHLORIDE (CCL4) IN THE CEREBRUM OF WISTAR RATS

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Carbon tetrachloride is a colorless, highly volatile liquid with a sweetish odor similar to chloroform used in refrigerants, propellants and industrial solvents. CCl4 is rapidly absorbed via oral, inhalation and dermal routes, distributing to the brain and other organs. It has been reported that CCl4 can metabolize to give out free radicals inducing oxidative stress and lipid peroxidation which can ultimately alter brain structure, and impair learning and memory, even at low doses. This study was aimed at invest gating the effect of CCl4 on the cerebrum of adult Wistar rats. Eighteen adult Wistar rats weighing 140 g to 150 g were used in this study. They were randomized into three (3) groups of six (6) rats each. Group A served as the control and received 1ml of di tilled water daily to compensate for stress of administration, whereas, rats in group B received 1.5mg/kg body weight of CCl4 and group C received 3mg/kg body weight of CCl4. All administration intraperitoneally lasted for a period of 28 days. The body weights of the rats were recorded daily. After the end of the experimental period, the rats were sacrificed by cervical dislocation and the organ (cerebrum) weight was recorded. The parameters accessed include cerebral antioxidant enzymes (SOD, CAT, GPx and GSH), MDA concentration and the histology of the cerebrum using Haematoxylin and Eosin staining technique. Data was analyzed using SPSS/IBM statistical package version 20. Results obtained showed no significant change (p>0.05) in the initial body weight of rats across experimental groups. However, a significant decrease (p<0.05) in final body weight and weight change of rats in group B (1.5 mg/kg bw CCl4) and C (3 mg/kg bw CCl4) when compared to control. No significant change (p>0.05) was observed in the cerebral weight of rats across experimental groups. However, a significant increase (p<0.05) was observed in relative cerebral weight of rats in group B (1.5 mg/kg bw CCl4) and C (3 mg/kg bw CCl4) when compared to control. A significant decrease (p<0.05) was observed in cerebral SOD, CAT, GPx and GSH activity of rats in group C (3 mg/kg bw CCl4) when compared to control. A significant increase (p<0.05) was observed in MDA concentration of rats in group B (1.5 mg/kg bw CCl4) and C (3 mg/kg bw CCl4) when compared to control. Histological findings revealed normal archictecture of the cerebrum in group A, whereas cytoplasmic vacoulizaion were seen in the granular cells of rats in group B and C. In conclusion, findings from this study shows that CCl4 induced neurotoxic effect on the cerebrum via inducing oxidative stress and altering the architectural integrity of the cerebrum.
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co-supervisor

HISTOLOGICAL CHANGES IN THE LARYNX AND SOME HAEMATOLOGICAL AND BIOCHEMICAL CHANGES IN WISTAR RATS FOLLOWING EXPOSURE TO CERAMICS DUST

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Exposure to industrial dust has been linked to respiratory and systemic toxicity. Ceramics dust, a common occupational contaminant, contains particulate matter that may induce structural and biochemical alterations. This study aimed to investigate the histological changes in the larynx and some haematological and biochemical parameters in adult Wistar rats following exposure to ceramics dust. Twenty-four (24) adult Wistar rats with weight ranging from 120–200g were grouped into four groups (A, B, C and D). The rats in Group A served as the control, the rats in Groups B were exposed to 5g of ceramics dust (low dose), the rats in Group C were exposed to 10g of ceramics dust (medium dose) and the rats in Group D were exposed to 20g of ceramics dust (high dose) for a duration of 1 hour daily for 30 days. At the end of the exposure period, rats were sacrificed, laryngeal tissues harvested for histological assessment, and blood samples collected for haematological and biochemical analyses, including RBC, WBC, hemoglobin, urea, creatinine, and bicarbonate levels. Histology revealed dose-dependent inflammatory infiltration in exposed groups. Haematological analysis showed dose-dependent decrease in hemoglobin and hematocrit, with a more significant decrease in the WBC count of the high dust exposure (20g) when compared with the control group. Biochemical assessment indicated elevated urea levels and decreased bicarbonate levels, suggesting renal and systemic effects of ceramics dust. These findings indicate that ceramics dust exposure causes structural damage to the larynx and alters some haematological and biochemical parameters in Wistar rats. The study underscores the potential health risks of occupational ceramics dust exposure and highlights the need for protective interventions in industrial settings.
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co-supervisor

EVALUATION OF THE EFFECTS OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) ON FEMALE REPRODUCTION IN ADULT WISTAR RATS

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The increasing recreational use of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") among women of reproductive age raises critical concerns regarding fertility and pregnancy outcomes. This study investigated the reproductive and developmental toxicity of MDMA in adult female Wistar rats, focusing on hormonal regulation, oxidative stress, histopathology, and gestational effects following pre-gestational and gestational exposure. A total of 140 Wistar rats (120 females, 20 males) were assigned to pre-gestational (Category A) and gestational (Category B) protocols. Treated groups received oral MDMA at 80 mg/kg and 160 mg/kg, while controls received distilled water. Serum levels of FSH, LH, PRL, estradiol, progesterone, and testosterone were measured alongside oxidative stress markers (SOD, CAT, GPx, MDA) and histological analyses of the pituitary, ovaries, and uterus. Data were analyzed using one-way ANOVA with LSD post hoc test (p < 0.05).
MDMA induced dose-dependent reductions in body and reproductive organ weights, likely due to serotonergic suppression of appetite, oxidative stress, and mitochondrial dysfunction. Hormonal assays revealed significant disruption of the hypothalamic-pituitary-gonadal (HPG) axis, including reduced LH (p = 0.02), elevated estradiol (p = 0.00), and progesterone (p = 0.05). A biphasic testosterone response was observed: reduced in the 80 mg/kg group (0.48 ± 0.00 ng/mL vs. 1.12 ± 0.14 ng/mL in controls) and elevated in the 160 mg/kg group (1.48 ± 0.09 ng/mL; p = 0.00), suggesting dysregulation of androgen synthesis via theca cell dysfunction or disrupted HPG feedback. Reproductive outcomes mirrored endocrine alterations. Pre-gestational exposure reduced conception rates (100% in controls vs. 20% and 0% in treated groups). Gestational exposure impaired implantation, fetal viability, and growth, leading to increased resorptions, intrauterine growth restriction, stillbirths, and postnatal abnormalities. Biochemical assays revealed dose-dependent suppression of antioxidant enzymes and altered lipid peroxidation, indicating oxidative damage in ovarian and uterine tissues.
Histopathological evaluation showed progressive degeneration: the pituitary exhibited chromophobe predominance and vacuolation; ovaries showed follicular atresia, degeneration, and vascular injury; and uterine tissues demonstrated glandular atrophy, edema, inflammation, and myometrial disruption. These structural changes aligned with the observed biochemical and hormonal abnormalities. In conclusion, MDMA exposure before or during pregnancy disrupts female reproductive function in a dose-dependent manner. It impairs fertility, alters endocrine signaling, induces oxidative stress, and causes tissue-specific toxicity, with profound consequences for implantation and fetal development. These findings reinforce the public health risks of MDMA use during reproductive years and the need for targeted reproductive toxicology awareness.

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co-supervisor

ROLE OF RUTIN IN THE ATTENUATION OF LEAD- INDUCED HIPPOCAMPAL TOXICITY IN WISTAR RATS

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Lead exposure is thought to be harmful and has been linked to behavioral abnormalities, hearing deficiencies, neuromuscular weakness, and decreased cognitive abilities in humans. Flavonoids have beneficial biological activities such as antioxidant, anti-inflammatory, anti-allergic, antiviral, anticarcinogenic effects. Flavonoids are the most recognised phytochemicals that function as antioxidants. Flavonoids' antioxidant activity includes suppressing ROS generation by inhibiting enzymes, scavenging free radicals, and regulating antioxidant defenses. Rutin is a typical dietary flavonoid that is nontoxic and naturally derived. It has a variety of beneficial biological properties including anti-cancer, antioxidant, antidiabetic, anti-inflammatory, anti-bacterial, anti-fungal, neuroprotective, cardioprotective, hepatoprotective, nephroprotective, haematoprotective, anti-arthritis, anthelmintic effects. Accordingly, this study was designed to investigate the possible attenuative effects of Rutin on lead-induced neurotoxicity in Wistar rats. After purchase and acclimatization, the Wistar rats were weighed and divided into six equal groups (control and treatment groups). Group A (Control) was administered 1 ml dH2O/day. Group B (Pb) was administered 100 mg/kg body weight (BW) of Pb acetate only. Group C (RUT1 + Pb) was administered 50 mg/kg BW of Rutin and 100 mg/kg BW of Pb acetate. Group D (RUT2 + Pb) was administered 100 mg/kg BW of Rutin and 100mg/kg of Pb acetate. Group E (RUT1) was administered 50 mg/kg BW of Rutin only and Group F (RUT2) was administered 100mg/kg BW of Rutin only. The administration, via an orogastric tube, lasted for 28 days and rats were fed with standard rat chow and had free access to water throughout the entire study period. All Rutin administration pre-treatment were done one hour before Lead. Animals were weighed and neurobehavioral activity (Novel object recognition test) was evaluated. The rats were then sacrificed for sample collection, and the hippocampus was harvested for assessment of antioxidant activity and histological alterations . The findings showed that the Pb group showed a significant decrease (p<0.05) in final body weight (FBW) compared to the control and Rutin treated groups, which showed a greater FBW. Neurobehavioral findings revealed that rats in the Pb group had significantly lower neurobehavioral function when compared to Control and Rutin treated groups. The Pb alone groups demonstrated oxidative stress (low antioxidant activity and increased lipid peroxidation), whereas the Control and Rutin treated groups had significant increase (p<0.05) in antioxidant activity. Histological findings shows altered morphology with the presence of vacuoles and pyknotic nuclei in the CA1 region of the Pb treated group, however the pretreated groups showed a healthier tissue architecture when compared to lead only treated group. In conclusion, the findings showed that Rutin was not toxic to the animals and protected against Pb toxicity.
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co-supervisor

INHIBITION OF CEREBELLAR DYSFUNCTION IN MANGANESE CHLORIDE-EXPOSED WISTAR RATS TREATED WITH VANILLIN

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Cerebellar dysfunction, marked by impaired coordination and balance, often result from toxic or degenerative damage to cerebellar neurons. Excessive exposure to manganese chloride, a neurotoxic compound, disrupts neuronal integrity through oxidative stress and inflammation, leading to motor and structural deficits. Vanillin, a natural phenolic compound with strong antioxidant and anti-inflammatory properties, has shown potential in mitigating such neurotoxic effects. This study therefore investigated the protective effect of vanillin against manganese chloride–induced cerebellar toxicity in Wistar rats. Forty-eight (48) Wistar rats were randomly assigned into six groups (A-F). Group A rats served as the control group; Group B rats were administered 10 mg/kg body weight of manganese chloride; Group C rats were administered 20 mg/kg body weight of vanillin and 10 mg/kg body weight of manganese chloride; Group D was administered 40 mg/kg body weight of manganese chloride and 40 mg/kg body weight of vanillin; Group E was administered 20 mg/kg body weight of vanillin; Group F was given 40 mg/kg body weight of vanillin. All administrations lasted for twentyeight (28) days. Neurobehavioural activities were evaluated using the open field, movement initiation, step and string Tests. Results from the study revealed that rats exposed to manganese chloride exhibited significant (p<0.05) weight loss, motor deficit, impaired antioxidant defense, elevated lipid peroxidation and degeneration of Purkinje cells and molecular layer neurons. However, pre-treatment with Vanillin significantly (p<0.05) mitigated these manganese chloride-induced cerebellar alterations in Wistar rats. Overall, the findings from this study indicate that vanillin possesses strong antioxidant properties, supporting its potential as an effective therapeutic agent for the treatment and management of manganese chlorideinduced cerebellar dysfunction
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co-supervisor

EFFECT OF AQUEOUS EXTRACT OF Musa paradisiaca ONTHE KIDNEY OF ADULT WISTARRATS

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Musa paradisiaca (plantain) is widely used in traditional medicine and consumed as food, yet its renal safety profile remains poorly characterized. This study evaluated the dose dependent
effects of its aqueous extract on kidney function and oxidative stress in adult Wistar rats. Twenty-five rats were divided into five groups (A–E) and administered control, 100, 500, 750, and 1000 mg/kg of Musa paradisiaca extract orally for 16 days. Serumurea, creatinine, antioxidant enzymes—superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase(GPx)—and malondialdehyde (MDA) were assayed. Kidney weights, reno-somatic index(RSI), and histological features were evaluated. Serum urea increased significantly (p < 0.05) inratsreceiving 750 mg/kg and 1000 mg/kg extract compared with control. Antioxidant enzymeactivities (SOD, CAT, and GPx) declined notably at higher doses, whereas MDA levels hadnosignificantly, indicating absence of enhanced lipid peroxidation and oxidative stress. TheRSIwas elevated in the 1000 mg/kg group, although body weights were unaffected. Histological
sections showed preserved renal architecture across groups, suggesting functional rather than structural injury at higher doses. In conclusion the aqueous extract of Musa paradisiacaislargely safe at low to moderate doses but elicits biochemical signs of nephrotoxicity at higher concentrations. The findings justify the need for dosage regulation and caution in prolonged or high dose use of plantain based remedies
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co-supervisor

EFFECTS OF MEMANTINE ON NICKEL CHLORIDE INDUCED CEREBELLAR TOXICITY IN WISTAR RATS

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Nickel chloride (NiCl2) is a widespread environmental contaminant that causes neurotoxicity, with the cerebellum showing particular vulnerability due to its central role in motor coordination and high metabolic demands. Memantine, a non-competitive
N-methyl-D-aspartate (NMDA) receptor antagonist. It is hypothesized that its neuroprotective properties could be beneficial in the mitigation of cerebellar damage caused by nickel chloride. This study was aimed at investigating the effects of memantine on the nickel chloride induced cerebellar toxicity in wistar rats. Forty-eight rats were divided into eight groups: Control, nickel chloride only, high dose of memantine + nickel chloride, low dose of memantine + nickel chloride, high dose of memantine, low dose of memantine. The treatment protocol ran for 28 days. A served as control and received 1ml of distilled water daily to compensate for stress of administration, whereas, rats in group B received 2.5mg/kg of NiCl₂, rats in group C received 10mg/kg Og memantine(low dose) and 2.5mg/kg of NiCl₂, rats in group D received 20mg/kg of memantine (high dose) and 2.5mg/kg of NiCl₂, rats in group E received 10mg/kg of memantine (low dose) and rats in group F received 20mg/kg of memantine (high dose). Administration of memantine was done orally using an orogastric tube while the administration of nickel chloride was done via intraperitoneal injection. It lasted for 28days. The body weight of the rats were recorded daily. At the end of the experimental period, the rats were sacrificed by cervical dislocation and the organ( cerebrum) weight was recorded. The parameters accessed include cerebral antioxidant enzymes (SOD, CAT, GPx and GSH), MDA concentration and the histology of the cerebrum using
Hematoxylin and Eosin staining technique. Results obtained showed no significant change (p>0.05) in the initial body weight and final body weight. A significant decrease (p<0.05) was observed in the weight change of rats in group B when compared to control, however, a significant increase (p<0.05) was observed in the weight of groups C and D when compared to group B. No significant change (p>0.05) was observed in the cerebellar and relative cerebellar weight of rats across experimental groups. A significant decrease (p<0.05) was observed in cerebellar SOD, CAT, GPx and GSH activity of rats in group B (2.5 mg/kg bw. NiCl2) when compared to the control. A significant increase (p>0.05) in cerebellar MDA concentrations was observed in the weights of rates in group B (2.5 mg/kg bw. NiCl2 ) when compared with group A. Severe histological alterations in the cerebellum of nickel-chloride exposed rats were observed. However, pre-treatment with memantine mitigated the adverse effects induced by NiCl2. In conclusion, findings from this study shows that memantine exerted antioxidant properties as well as mitigating the histological alterations in the cerebellum.
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co-supervisor

EFFECT OF AQUEOUS EXTRACT OF LAWSONIA INERMIS LEAVES ON LEAD ACETATE-INDUCED LIVER DAMAGE IN ADULT WISTAR RATS.

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Lawsonia inermis commonly known as henna has been used traditionally, especially in ayurvedic medicine, for various conditions including liver ailments, and reported to have hepatoprotective properties. This study aims to study the effect of aqueous extract of L.
inermis leaves in acute ethanol induced hepatic damage in adult Wistar rats. Thirty (30) female rats were equally divided into five (5) groups (I-V). Group I which served as control received distilled water for 28 days. Group II received Lawsonia inermis for 28 days. Group
III received 100 mg/kg of lead acetate only for 28 days. Group IV simultaneously received 100 mg/kg of lead acetate and treated with 70mg/kg of silymarin for 28 days to serve as reference drug. Group V simultaneously received 100mg/kg of lead acetate and treated with
200mg/kg of L. inermis for 28 days. Group VI simultaneously received 100mg/kg of lead acetate and treated with 400mg/kg of L. inermis for 28 days. Group VII received 400mg/kg of L. inermis and followed with 100mg/kg of lead acetate after 30 minutes for 28 days. All
animals were sacrificed on the twenty ninth (29th) day. Body weight changes and liver body weight index were determined. Liver tissues were collected for assessment of enzymes concentration, and also for haematoxylin and eosin staining. Body weight increased in all
groups from initial mean weight of 180.1 g, though significantly (p<0.05) only in Group IV, Group V and Group VI. Liver body weight index was highest in Group I, and was significantly (p<0.05) different from Group III and Group V. Lead administration reduced level of enzyme aspartate Transferase significantly and increased the value of total bilirubin significantly of (P<0.05) although decrease was seen in enzymes like unconjugated bilirubin, alkaline phosphate and alanine Transferase and increased in conjugated bilirubin but these
were not significant to (P<0.05) H&E staining revealed attenuation of the effects of Lead administration by the extract and silymarin, though the extract proved more effective at 400 mg/kg dose and duration of 28 days. Promising result was also observed in the group that
received 200mg/kg dose over a duration of 28 days.
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