Therapeutic potential of policosanol in the concurrent management of dyslipidemia and non-alcoholic fatty liver disease

Background High-fat diet (HFD) possesses a major cause of cardiovascular disease, and hepatosteatosis. Unfortunately, long-term use of statins has a theoretical possibility of worsening of hepatic histology in the patients with non-alcoholic fatty liver disease (NAFLD). The objective of the study was to explore hepatoprotective potential of policosanol as an alternative to statins in experimental NAFLD. For the same, young male Wistar rats were fed with HFD for 8 weeks to induce NAFLD. 48 adult Wistar rats were distributed into six investigational groups: normal control, HFD control, and four treatment groups, receiving policosanol (50 and 100 mg/kg/day), atorvastatin (30 mg/kg/day), and silymarin (100 mg/kg/day) for 8 weeks along with HFD. Result HFD consumption caused profound hepatotoxicity evident by hepatic oxidative stress, increased Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), Alkaline phosphatase (ALP), and bilirubin content. Treatment with policosanol (100 mg/kg) markedly reduced the elevated SGOT, SGPT, and ALP levels in HFD-fed rats. Moreover, policosanol significantly reduced hepatic oxidative stress manifest by reduced malondialdehyde (MDA) and increased glutathione (GSH) level. The treatment with policosanol (100 mg/kg) was found to be more active in attenuating the HFD-induced hepatotoxicity as compared to policosanol (50 mg/kg) and atorvastatin (30 mg/kg). Moreover, we observed that the hepatoprotective potential of policosanol was comparable to the silymarin. Conclusions The results of the study clearly indicated that the policosanol could be considered an intriguing approach for the treatment of NAFLD.

Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats

Background Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals’ relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats’ relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium’s inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.

Toxicological Indices of Wistar Rats Fed Formulated Chaw of Telfairia occidentalis Planted on Crude Oil Contaminated and Remediated Soil

Toxicological indices of wistar rats fed formulated chaw of Telfairia occidentalis planted on crude oil contaminated and bioremediated soil was studied. Farmland, measuring 18 m2 was divided into three lots of 4 m2 and 2 m space was allowed between each lot (A, B and C). Two lots were polluted, subjected to 16 weeks of bioremediation and viable seeds of T. occidentalis were planted and grown for 28 days. The harvested vegetable leaves were analyzed. Leaves from natural attenuated soil showed high concentration of both aliphatic and polycyclic aromatic hydrocarbons with values of 9.34+0.03 mg/kg and 9.18+0.05 mg/kg for C36 and Fluoranthene respectively, while the bioaugmented soil had Lead as the highest heavy metal with a value of 0.10+0.02 g/100g. Four groups, of 9 rats each (totalling 36 rats) of adult males and females, wealing males and females were subsequently sub-grouped into 3 and allowed to acclimatize for a period of 1 week. These animals were fed formulated rat chaw of 50% dry weight of T. occidentalis, from the three lots (control, bioaugmented and natural attenuated soil) for a period of 28 days. Assay of animals’ toxicological index showed elevated concentrations of alkaline phosphatase, alanine and aspartate aminotransferases, urea and creatinine in their sera. A slight increase in serum amylase activity was recorded, while concentrations of their haemoglobin and Packed Cell Volume (PCV) reduced. The obtained results from these biomarkers were confirmed by the histopathological sections of the animal organs.

Changes in the Serum Levels of Estradiol and Changes in Expression of Estrogen Receptor Alpha in the Bone Tissue of Ovariectomized Wistar Rats

Estradiol is an estrogen steroid hormone and is produced basically within the follicles of the ovaries. The decrease in serum estrogens concentration at menopause disrupts the metabolic balance, changes the lipid profile leading to visceral obesity, which caused an increase in serum estradiol levels, through aromatase activity. Estrogen deficiency also is a reason for the development of osteoporosis.We investigated the serum estradiol levels and changes in bone alpha estrogen receptor expression in ovariectomized rats. For this purpose, we used 20 female Wistar rats at reproductive age - 2 months divided into 2 groups: group 1 (G1)-10 animals were ovariectomized and group 2 (G2)-10 of which were sham-operated. All animals of G1 showed weight gain compared to group G2. The results showed that the values of serum 17β-estradiol in rats of G1 statistically increased compared to G2 (p <0.05). Immunohistochemical analysis revealed no difference in estrogen receptor expression between the both groups. Histomorphological analysis of femur from G1 showed the presence of pronounced osteoporosis. Ovariectomy led to the development of obesity, which caused an increase in serum estradiol levels, through aromatase activity, but this process did not prevent bone tissue from developing osteoporosis.

Estrogenic Effect of Bambusa arundinacea, Trichosanthes dioica and Punica granatum on Rats

Background: Phytoestrogens have recently become a hot topic among scientists. Phytoestrogens’ estrogen-like properties have led to their widespread use in the reproductive system. The aim of this research was to see whether the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum had any estrogenic activity in female wistar rats. Methods: In female wistar rats, the estrogenic effect was studied using a uterotropic assay, vaginal cytology and vaginal opening. In ovariectomized immature and mature female wistar rats, a 400 mg/kg body weight (b.w.) dose of ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum was given. Result: When compared to ovariectomized control rats, the uterine wet weight increased significantly. The estrogen-treated rats had only cornified epithelial cells, indicating the existence of oestrogen, as well as 100% vaginal opening. At 400 mg/kg b.w., the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum demonstrated promising estrogenic activity, as evidenced by uterotropic assays, vaginal opening measurements and histopathological changes. As a result of this research, it’s possible to infer that the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum play an important role in estrogenic activity in female rats.

Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

Histopathology and Renal Function in Wistar Rats after Intravascular Injection of Iodinated Contrast Media Iohexol and Iopamidol

This research aimed to analyze the histopathology (tubular necrosis and proteinaceous casts) and renal function (SCr and BUN) differences of male Wistar strain white rats (Rattus norvegicus) after intravascular injection of iodinated contrast media Iohexol and Iopamidol. This research is an experimental laboratory with a post-test only control group design. Male Wistar rats that fit the criteria were divided into three groups by random sampling technique: Control (K), Treatment 1 (P1, Iohexol 350 mg iodine/mL), and Treatment 2 (P2, Iopamidol 370 mg iodine/mL). Iohexol and Iopamidol were injected at a dose of 1600 mg iodine/kg BW. The histopathology differences were observed under a light microscope with a magnification of 400x, which were analyzed semi-quantitatively through slides formed by the paraffin method and H&E staining. SCr and BUN levels were checked using an automatic analysis machine with blood samples taken through the cardiac ventricle. Kruskal-Wallis test (α= 0.05) on renal histopathology scores, both tubular necrosis and protein casts showed Asymp. Sig. value > 0.05, which means there is no significant difference between the groups (K, P1, and P2). Kruskal-Wallis test (α= 0.05) on SCr levels also showed the Asymp. Sig. value > 0.05 and One-Way ANOVA Comparative Test on BUN levels showed the Sig. value > 0.05 which means there is no significant difference in renal function between the groups. This study proved no difference in histopathology and renal function in Wistar rats after injection of iodinated contrast media Iohexol and Iopamidol.

Healing Effects of Iranian Dwarf Elder on Full-thickness Epidermal Thermal Injury in Wistar Rats

Background: Wound healing is a physiologic process that cells and tissues react when the skin is exposed to thermal injury. The inflammatory process has ‎essential effects on wound healing that includes coordination between immunological and biological responses. Chemical and herbal medicines are locally or systemically administrated to help wound healing. Herbal medicines have become more prevalent in recent years due to fewer side effects. Dwarf elder is used to treating inflammation and has been reported to possess antibacterial and antioxidant activities. This plant is also effective against burns, wounds, eczema, and infection. Objectives: In this study, we evaluated the topical application of dwarf elder on full-thickness epidermal thermal wounds in Wistar rats. Methods: Thirty adult male Wistar rats of about 300 g were used. The rats were randomly divided into three groups: Control group, vehicle group treated with an ointment base, and treatment group treated with elder ointment 10%. The animals were anesthetized and were created burn wounds with an area of 1 cm2 using the Meyer method. After 21 days, the wounds were photographed with a Canon camera. The wound area and healing degree were calculated. Slides were stained with H&E and examined by light microscopy and GraphPad Prism software. Data were analyzed by SPSS software using ANOVA and Tukey’s test. The significance level was considered at P < 0.05. Results: The wound area on the 21st day was significantly lower in the treatment group than in the control and vehicle groups. The epithelium thickness (μm) was significantly higher in the treatment group than in the control and vehicle groups. The blood vessels were significantly higher in the treatment group than in the other groups. Conclusions: The study showed that elder extract could be an effective remedy to repair and heal thermal injury and burn wounds.