Antidiabetic and Liver Histological and Ultrastructural Effects of Cynara scolymus Leaf and Flower Head Hydroethanolic Extracts in Nicotinamide/Streptozotocin-Induced Diabetic Rats.

This study aims to investigate the effect of hydroethanolic extracts of Cynara scolymus (C. scolymus) leaf (CLHE) and C. scolymus flower (CFHE) on the hepatic histopathological lesions and functional biochemical changes induced by type 2 diabetes mellitus (T2DM). The rat model of T2DM was induced by intraperitoneal injection of streptozotocin (STZ) in a dose of 60 mg/kg for 15 minutes following nicotinamide (NA) (60 mg/kg). The rats were allocated into four groups: group 1 (negative control), group 2 (diabetic control), group 3 (diabetic rats supplemented with 100 mg/kg/day CLHE), and group 4 (diabetic rats supplemented with 100 mg/kg/day CFHE). Treatment with CLHE and CFHE, for the study duration of 28 days, significantly improved the deteriorated hepatic glycogen content, glycogen phosphorylase, glucose-6-phosphatase activities, serum fructosamine levels, lipid profile, aspartate transaminase activities, and alanine transaminase activities as well as serum insulin and C-peptide levels. The elevated liver lipid peroxidation and the decreased activities of superoxide dismutase and glutathione peroxidase were significantly alleviated. The elevated expression of the proinflammatory cytokine tumor necrosis factor-α in the liver of diabetic rats was significantly reduced by treatments with CLHE and CFHE. NA/STZ-induced T2DM exhibited hepatic histopathological changes in the form of disordered hepatocytes, cytoplasm dissolution, and mononuclear leukocytic infiltration. The electron microscopic ultrastructure study revealed damaged mitochondria with ill-defined cristae and fragmentation of the rough endoplasmic reticulum. Treatments with CLHE and CFHE remarkably amended these histopathological and EM ultrastructural changes. In conclusion, both CLHE and CFHE may have antidiabetic and improvement effects on the liver function and structural integrity, which may be mediated, at least in part, via suppression of inflammation and oxidative stress and enhancement of the antioxidant defence system.

Effect of gervital in attenuating hepatotoxicity caused by methotrexate or azathioprine in adult albino rats.

Methotrexate (MTX) and azathioprine (AZA) are chemotherapeutic, antimetabolic, and immunosuppressive agents with substantial risks such as oxidative lesions to the liver. This study examined the effect of grape seed extract (GSE; gervital) in attenuating hepatotoxicity caused by MTX or AZA treatment. Rats were divided into six groups (six rats per group): Group I, normal control group; Group II, GSE (150 mg/kg/day); Group III, MTX (8 mg/kg/week); Group IV, AZA (15 mg/kg/day); Group V, GSE (150 mg/kg/day) + MTX (8 mg/kg/week); and Group VI, GSE (150 mg/kg/day) + AZA (15 mg/kg/day). After 35-day experimental period, all rats were sacrificed and blood was collected for biochemical study and hemoglobin (Hb) assessment. The liver was weighed and triaged for histological, ultrastructural, and biochemical studies. MTX and AZA treatment decreased Hb levels, increased relative liver weight, increased the activity of glutamate pyruvate transaminase (ALT) and glutamate oxaloacetate transaminase (AST) aminotransferase (ALT) and aspartate aminotransferase (AST) values, and displayed histopathological and ultrastructural alterations. These changes included the disorganization of hepatocytes, pyknosis, karyolysis of some nuclei, and mononuclear leukocytic infiltration. The liver with significant oxidative stress (OS) showed decreased reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and increased malondialdehyde (MDA) levels. In contrast, GSE administration ameliorated ALT, AST, and all histopathological and ultrastructural changes. GSE treatment also reduced MDA levels but increased the antioxidant parameters. In conclusion, it was concluded that GSE supplementation could be considered as a promising antioxidant in reducing OS, histopathological and ultrastructural alterations induced by MTX and AZA.

Melissa officinalis L. ameliorates oxidative stress and inflammation and upregulates Nrf2/HO-1 signaling in the hippocampus of pilocarpine-induced rats.

Epilepsy is characterized by recurrent epileptic seizures, and its effective management continues to be a therapeutic challenge. Oxidative stress and local inflammatory response accompany the status epilepticus (SE). This study evaluated the effect of Melissa officinalis extract (MOE) on oxidative stress, inflammation, and neurotransmitters in the hippocampus of pilocarpine (PILO)-administered rats, pointing to the involvement of Nrf2/HO-1 signaling. Rats received PILO via intraperitoneal administration and were treated with MOE for 2 weeks. MOE prevented neuronal loss; decreased lipid peroxidation, Cox-2, PGE2, and BDNF; and downregulated glial fibrillary acidic protein in the hippocampus of PILO-treated rats. In addition, MOE enhanced GSH and antioxidant enzymes, upregulated Nrf2 and HO-1 mRNA abundance, and increased the nuclear translocation of Nrf2 in the hippocampus of epileptic rats. Na+/K+-ATPase activity and GABA were increased, and glutamate and acetylcholine were decreased in the hippocampus of epileptic rats treated with MOE. In conclusion, MOE attenuated neuronal loss, oxidative stress, and inflammation; activated Nrf2/HO-1 signaling; and modulated neurotransmitters, GFAP, and Na+/K+-ATPase in the hippocampus of epileptic rats. These findings suggest that M. officinalis can mitigate epileptogenesis, pending further studies to explore the exact underlying mechanisms.

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.

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

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.