Manal Abdul-Hamid

Prenatal and perinatal acrylamide disrupts the development of cerebellum in rat: Biochemical and morphological studies.

Acrylamide is known to cause neurotoxicity in the experimental animals and humans. The literature on its neurotoxic effect in the adult animals is huge, but the effect of acrylamide on the embryonic and postnatal development is relatively less understood. The present study examined its effects on the development of external features and cerebellum in albino rats. Acrylamide was orally administered to non-anesthetized pregnant females by gastric intubation 10 mg/kg/day. The animals were divided into three groups as follows. (1) Group A, newborn from control animals; (2) Group B; newborns from mothers treated with acrylamide from day 7 (D7) of gestation till birth (prenatal intoxicated group); (3) Group C; newborns from mothers treated with acrylamide from D7 of gestation till D28 after birth (perinatally intoxicated group). Acrylamide administered either prenatally or perinatally has been shown to induce significant retardation in the newborns’ body weights development, increase of thiobarbituric acid-reactive substances (TBARS) and oxidative stress (significant reductions in glutathione reduced [GSH], total thiols, superoxide dismutase [SOD] and peroxidase activities) in the developing cerebellum. Acrylamide treatment delayed the proliferation in the granular layer and delayed both cell migration and differentiation. Purkinje cell loss was also seen in acrylamide-treated animals. Ultrastructural studies of Purkinje cells in the perinatal group showed microvacuolations and cell loss. The results of this study show that prenatal and perinatal acrylamide or its metabolites disrupts the biochemical machinery, cause oxidative stress and induce structural changes in the developing rat cerebellum.

Amelioration of alloxan-induced diabetic keratopathy by beta-carotene

This study was undertaken to assess the anti-keratopathy activity of β-carotene in experimentally-induced diabetic animal model. The rats were divided into four groups as following: G1, normal control group; G2, β-carotene control group (50 mg/kg b.wt.); G3, diabetic group which was injected intraperitoneally with a single dose (100 mg/kg b. wt) of alloxan (ALX) and G4, diabetic rats treated with β-carotene which was injected with ALX as G3, and then received a daily oral dose of β-carotene (50 mg/kg b.wt.) for 3 months. ALX injection caused elevated levels of serum glucose in diabetic group. Moreover, histopathology revealed relatively thick corneal epithelium, ill-defined Bowmans membrane, widely spaced stromal layers and relatively thick Descemets membrane. Electron microscopic studies showed vacuolated cytoplasm, partial loss of hemi-desmosomes and disorganized collagen fibrils with focal lysis of stromal layer. Oral gavage of β-carotene to diabetic rats for 3 months significantly decreased serum glucose level and ameliorated histopathological, immunohistochemical and ultrastructural results. Consequently, β-carotene exerted anti-keratopathy effects and ameliorated the corneal changes in diabetic rats via its hypoglycemic and antioxidant mechanisms.

Ameliorative effect of Pimpinella anisum oil on immunohistochemical and ultrastuctural changes of cerebellum of albino rats induced by aspartame.

Abstract The study aims to investigate the protective effect of Pimpinella anisum oil on aspartame (ASP) which resulted in cerebellar changes. The rats were divided into four equal groups: Group 1: (control group): served as control animals. Group 2: control P. anisum oil received .5 mL/kg/d/b wt. once daily. Group 3 (ASP group): received daily 250 mg/kg/b wt. of ASP dissolved in distilled water and given orally to the animals by intra-gastric tube for 2 months. Group 4: received .5 mL/kg/b wt. of prophylactic P. anisum oil once daily, followed by ASP after 2 h for 2 months. The histopathological approach revealed marked changes in the Purkinje cells, myleinated nerve fibers and granular cells of ASP-treated animals. Some of these cells appeared with deeply stained cytoplasm. Ultrastructural examination showed Purkinje cells with dilated rough endoplasmic reticulum and condensed mitochondria. Granular cells appeared with less c nuclei and surrounded by dissolution of most Mossy rosettes structures. Most myelinated nerve fibers showed thickening of myelinated sheath and others showed splitting of their myelin sheath. The histopathological, immunohistochemical and ultrastructural alterations were much less observed in concomitant use of P. anisum oil with ASP. Cerebellar cortex is considered target areas of ASP neurotoxicity, while P. anisum oil, when used in combination with ASP displays a protective action against neurotoxicity.

Intervention of ginger or propolis ameliorates methotrexate-induced ileum toxicity.

The long-term clinical use of methotrexate (MTX) is restricted due to its severe intestinal toxicity. The protective effect of ginger or propolis on the toxicity induced by MTX is relatively less understood, so the possible protective effect of ginger or propolis, used separately, was investigated. A total of 60 male albino rats were divided into six groups as follows: (1) control group; (2) ginger group; (3) propolis group; (4) MTX group; (5) ginger + MTX group; and (6) propolis + MTX group. The present results show that MTX caused ileum injury, including shortening and fusion of the villi, inflammatory cell infiltration and goblet cell depletion. Administration of ginger or propolis ameliorated the MTX-induced ileum injury as shown by histological, immunohistochemical and ultrastructural investigations and statistical analysis. This is revealed by intact villi, which shows marked increase in brown colouration of proliferating cell nuclear antigen positive nuclei in the crypts region, improvement in the number of goblet cells and brush border length of ileum. The current results conclude the efficacy and safety of ginger and propolis, which may be due to their antioxidant properties.

Effect of diethylcarbamazine citrate and omega-3 fatty acids on trimellitic anhydride-induced rat skin allergy

BACKGROUND Diethylcarbamazine citrate (DEC) is the drug most widely used in the treatment of lymphatic filariasis. Omega-3 fatty acids (ω-3 FAs) are essential polyunsaturated fatty acids and commonly found in marine oils. Both have been applied in treatment of inflammatory diseases but anti-allergic effects should be investigated. OBJECTIVE The present study was performed to test the effect of both DEC and ω -3 FAs on Trimellitic anhydride (TMA) - induced rat skin allergy. METHODS In vivo experiment was executed in white albino rats using 100 and 600 mg/ Kg body weight of DEC and ω-3 FAs, respectively in treatment. Ear thickness of sensitized rats to TMA was monitored after challenge. Blood eosinophilia was determined using differential leukocyte count while the appearance of mast cells, eosinophils and collagen fibers in skin tissue were investigated using specific stains. Colorimetric assay of NO was performed in homogenized ears, while expression of inducible nitric oxide synthase (iNOS) was detected using immunohistochemistry. RESULTS Ear thickness showed a significant (p < 0.05) reduction in both of DEC and ω-3 FAs treated groups. Blood eosinophilia and skin eosinophils were significantly (p < 0.001) decreased by DEC and ?-3 FAs, while the decrease of skin mast cells was only significant (p < 0.01) when ω-3 FAs applied. The expression of iNOS and intensity of stained collagen fibers were decreased obviously by ω-3 FAs but less by DEC treatment. Histopathological observations were more normal in ω-3 FAs than DEC treated groups. CONCLUSION ω-3 FAs was more potent antiallergic substance against TMA-induced dermatitis than DEC.

The antifibrogenic effect of etanercept on development of liver cirrhosis induced by thioacetamide in rats

ABSTRACT Liver cirrhosis is an elevating cause of morbidity and mortality worldwide. TNF-α/TNF-R1 signal is implicated in progression of many liver diseases. This study provides histological and ultrastructural view that clarifies the effect of etanercept, a TNF-α inhibitor, on development of thioacetamide (TAA)-induced liver cirrhosis and the accompanied hemosiderosis in rats, highlighting the implication and distribution pattern of hepatic TNF-R1. Sixty male albino rats (Rattus norvegicus) were equally randomized into three groups. Group I served as the control. Liver cirrhosis was triggered in the other two groups by intraperitoneal injection of TAA twice a week for five months. Group II received TAA only, while group III subcutaneously injected with etanercept one hour before TAA, along five months. At the end of the experiment, blood was collected for biochemical analysis and livers were excised for histological, immunohistochemical, and electron microscopical preparations. Rats treated with TAA only developed hepatic cirrhosis accompanied by massive deposition of hemosiderin; strong and widespread expression of hepatic TNF-R1 in sinusoidal endothelial cells (SECs), Kupffer cells (KCs), and many hepatocytes; and frequent appearance of fibrogenic, plasma, and mast cells, at the ultrastructural level. By contrast, administration of etanercept diminished the expression of TNF-R1, attenuated the accumulation of collagen and hemosiderin, and preserved the hepatic histoarchitecture. In conclusion, TNF-α signal via TNF-R1 may be implicated in the mechanism of fibrogenesis and the associated hemosiderosis. Etanercept may provide a promising therapeutic approach not only for attenuating the progression of fibrogenesis, but also for hepatic iron overload-associated disorders.

Protective effect of ellagic acid against cyclosporine A-induced histopathological, ultrastructural changes, oxidative stress, and cytogenotoxicity in albino rats

ABSTRACT Cyclosporine A (CsA) is an immunosuppressor agent, which is most frequently used in transplant surgeries and in the treatment of autoimmune diseases. This study was undertaken to investigate the protective effects of ellagic acid (EA) against CsA-induced testicular histopathology and ultrastructure changes, oxidative stress, and cytogenotoxicity in male albino rats. Rats were divided into six groups; the first group was used as a control, the second group received a subcutaneous injection of slightly alkaline solution, the third group received olive oil orally, the fourth group was injected subcutaneously with EA at a dose of 10 mg/kg b. wt./day, the fifth group was treated with CsA as oral solution at a dose of 15 mg/kg b. wt for 30 days, and the sixth group was treated with CsA simultaneously with EA. Treatment with EA simultaneously with CsA resulted in significant protection. The positive control animals taking CsA alone showed marked histopathological, ultrastructure, and genetic manifestations accompanied by an elevated content of lipid peroxidation and marked reduction of catalase (CAT), peroxidase (Px) activity, and glutathione concentration in the homogenate of testis tissues. The toxic side effects in testis and bone marrow tissues were greatly ablated with a significant reduction in lipid peroxidation level and elevation in CAT and Px activities and glutathione concentration when using EA. Thus, EA may be used in combination with CsA to improve the histopathological, oxidative stress, and cytogenotoxicity parameters of testicular toxicity induced by CsA due to its antioxidant effects.

Protective effect of orange and grapefruit peel extracts against testicular toxicity induced by sulfasalazine in male albino rats

Introduction Sulfasalazine is a drug commonly used for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. However, the histological changes in the testes are not well defined. Also, orange and grapefruit peels are powerful antioxidants that have come into use recently for the treatment of infertility. Aim This study aimed to elucidate the histological, immunohistochemical, and ultrastructural changes in the testes after sulfasalazine treatment and evaluate the possible protective role of orange and grapefruit peel extracts. Materials and methods This study included 48 adult male albino rats divided into six equal groups: the control group (group I); the orange peel extract group (group II); the grapefruit peel extract group (group III); the sulfasalazine group (group IV); the sulfasalazine and orange peel extract group (group V); and the sulfasalazine and grapefruit peel extract group (group VI). At the end of the experiment (2 weeks), all animals were sacrificed and their testes were excised. Paraffin sections were prepared and stained with H&E and immunohistochemical staining was performed for proliferating cell nuclear antigen. Other pieces of the testis were used for ultrastructural study. Results Sulfasalazine was shown to affect the testes. The changes were in the form of irregular degenerated seminiferous tubules, germ cells, decrease in proliferating cell nuclear antigen, ultrastructural alterations of spermatogenic cells, and thickened basement membranes. These changes were present in some tubules in the testes. Treatment with orange or grapefruit peel extracts proved to improve these changes. Conclusion Sulfasalazine has deleterious effects on the structure of the testes and supplementation with orange or grapefruit peel extracts with sulfasalazine can overcome the toxicity of sulfasalazine on the testis and protect testicular tissue from the detrimental effects of sulfasalazine.