Hossam M. Omar

Minimal effect of acute experimental hepatitis induced by lipopolysaccharide/ d-galactosamine on biotransformation in rats

When administered with D-galactosamine, lipopolysaccharide endotoxins produce a good experimental animal model of hepatitis. This galactosamine plus endotoxin model has been used widely, but the acute effect of this fixed combination of two chemicals on hepatic and extrahepatic biotransformation has not been determined. Therefore, either 2 or 4 hr after a single intraperitoneal dose of 300 mg/kg galactosamine plus 30 micrograms/kg lipopolysaccharide was administered, serum, liver, kidney, intestine, and spleen were collected. Serum enzymes (alanine and aspartate aminotransferases, sorbitol dehydrogenase, and gamma-glutamyltranspeptidase) were elevated dramatically 2 and 4 hr after treatment. Cytochrome P450 monooxygenase activity toward benzo-[a]pyrene was increased in kidney 4 hr after treatment, whereas dealkylation of 7-methoxycoumarin or 7-ethoxyresorufin was unchanged in any tissue at either time point. An increase in UDP-glucuronosyltransferase activity toward 4-methylumbelliferone and 4-hydroxybiphenyl was noted in the intestine. Conjugation of 1-chloro-2,4-dinitrobenzene with glutathione was increased in intestine and spleen 2 hr after treatment. gamma-Glutamyltranspeptidase activity was unaltered in all tissues studied. Reduced glutathione concentrations were increased significantly by different amounts depending on which organs were studied 2 or 4 hr after treatment. These results indicate that galactosamine/lipopolysaccharide-induced liver injury is not accompanied by major effects on the examined biotransformation reactions.

Mycotoxins-Induced Oxidative Stress and Disease

Mycotoxins are pharmacologically active mold metabolites produced in a strain-specific way that elicit some complicated toxicological activities [1]. More than 300 secondary metabolites have been identified while only around 30 have true toxic properties [2]. The chemical structures of mycotoxins vary significantly, but they are low molecular mass organic compounds [3]. Mycotoxins are small and quite stable molecules which are extremely difficult to remove and enter the food and feed chain while keeping their toxic properties [4]. So, the occurrence of mycotoxins is regulated by legal limits in all developed countries [5]. Mycotoxin contamination of the feed and food is a global problem because more than 25% of world grain production is contaminated by mycotoxins [6]. The synthesis of mycotoxins by moulds is genetically determined and closely related to primary metabolic pathways, such as amino acid and fatty acid metabolism. However, the actual toxin production is modulated by environmental factors such as substrate composition and quality, humidity and temperature. The occurrence of mycotoxins in animal feed exhibits a geographic pattern, for example Aspergillus species meet optimal conditions only in tropical and subtropical regions, whereas Fusarium and Penicillium species are adapted to the moderate climate. Worldwide trade with food and feed commodities results in a wide distribution of contaminated material [7].

A Bradykinin Potentiating Fraction Isolated from the Venom of Egyptian Scorpion Buthus occitanus Induced Prostaglandin Biosynthesis in Female Guinea Pigs

Abstract A fraction with bradykinin potentiating activity was chemically isolated from the venom of the Egyptian scorpion Buthus occitanus. The pharmacological activity of the fraction (BPF) was bioassayed by its ability to potentiate added bradykinin on the isolated guinea pig ileum as well as its inhibitory activity on angiotensin converting enzyme. The mode of action of this fraction on gonads of immature female guinea pigs was studied. The fraction was i.p. injected 1 μg/g body weight for five times in animals (about, 150 g) at successive time intervals of 7 days each. Total body, ovarian, and uterine tissue weights were significantly increased as well as uterine total protein, RNA and cyclic nucleotides contents. Concomitantly, PGF2α level showed significant elevation in both uterine and ovarian tissues. The uterine tissue homogenates in vitro showed an enhancing effect in response to the added fraction (1 μg/ml) and bradykinin (1 μg/ml) for prostaglandin biosynthesis from radiolabelled precursor 14C-linoleic acid into its labelled metabolites: arachidonic acid, PGD2, TxB2, PGE2, PGF2α, and 6-keto PGF1α. This enhancement effect was abolished in the presence of BK inhibitor but the labelled PGF2α was still high. The results clearly indicate that the increase of PGs resulting from both in vivo and in vitro experiments may contribute to the inhibition of ACE and potentiation of exogenous and endogenous BK.

Possible Protective Effects of Quercetin and Sodium Gluconate Against Colon Cancer Induction by Dimethylhydrazine in Mice.

Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

Streptozotocin may provide protection against subsequent oxidative stress of endotoxin or streptozotocin in rats

Endotoxin lipopolysaccharide (LPS) and streptozotocin‐induced diabetes are known to cause oxidative stress in vivo. There is some evidence that a sublethal dose of LPS provides protection against subsequent oxidative stress. Because of its wide use as a diabetogenic agent, this study was undertaken to determine if streptozotocin can likewise provide a protective effect against further oxidative stress in rats. Female Sprague–Dawley rats were given streptozotocin (50 mg/kg intraperitoneally once) prior to exposure to either bacterial endotoxin from Salmonella abortus equii (5 mg/kg intraperitoneally) or three additional daily doses of streptozotocin (50 mg/kg intraperitoneally). One week after LPS or streptozotocin treatments, oxidative stress was determined by measuring changes in antioxidant activity (glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, glutathione S‐transferase, and γ‐glutamyltranspeptidase) and in concentrations of glutathione, nitrite, and thiobarbituric acid reactants in liver, kidney, intestine, and spleen. High levels of some antioxidants in the LPS‐control and streptozotocin‐control rats, in contrast to normal levels found in diabetes + LPS and multidose‐streptozotocin rats, suggest that streptozotocin, like LPS, may confer a protective effect against subsequent oxidative stress.

Time-dependent Morphological and Biochemical Changes following Cutaneous Thermal Burn Injury and Their Modulation by Copper Nicotinate Complex: An Animal Model

Background: Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). Objectives: To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. Materials and Methods: An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. Results: High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Conclusions: Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Acute Toxicity of the Mycotoxin Roridin E on Liver and Kidney of Rats

Abstract El-Din, M.O.H., El-Sawi, N.M. and Meki, A.R.M.A. 1997. Acute toxicity of the mycotoxin roridin E on liver and kidney of rats. J. Appl. Anim. Res., 12: 145–152. The effect of in vivo exposure to roridin E alone and in combination with linoleic add on rats was studied. Male rats treated with a sublethal dose (2 mg/kg body weight) of the trichothecene roridin E showed a significant increase in glucose-6-phosphatase of liver. Whereas, rats treated with roridin E plus linoleic acid (300 μmol/kg body weight) showed a significant decrease in the blood glucose and glutathione levels. The combined effect also resulted in a significant decrease in the levels of superoxide dismutase and glucose −6-phosphatase in the kidney together with a significant increase in the lipid peroxidation (TBARS) in the liver. In conclusion, treatment of rats by sublethal dose of roridin E alone did not caused any significant effect. However, co-administration of linoleic acid with roridin E resulted in increasing its toxicity.

Camel Whey Protein Protects B and T Cells from Apoptosis by Suppressing Activating Transcription Factor-3 (ATF-3)-Mediated Oxidative Stress and Enhancing Phosphorylation of AKT and IκB-α in Type I Diabetic Mice.

Background: Diabetes mellitus (DM) is associated with severe immune system complications. Camel whey protein (CWP) decreases free radicals (ROS) and modulates immune functions, but its effect on DM-impaired immune systems has not been studied. We investigated the impact of CWP on the immune system in a Type 1 diabetes mouse model. Methods: Three experimental groups were used: (1) non-diabetic control; (2) diabetic; and (3) CWP-treated diabetic mice. Results: Induction of diabetes by streptozotocin was associated with reduction of body weight and insulin level, increase in glucose level and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and reduction in IL-2 and IL-4 levels. Upregulated ATF-3 expression was followed by a marked elevation in ROS levels. Lymphocytes from diabetic mice exhibited increased apoptosis through decreased phosphorylation of AKT and IκB-α, increased infiltration of T cells in the spleen and thymus, and decreased B cell numbers in the spleen. Supplementation with CWP decreased the levels of proinflammatory cytokines, ROS, and ATF-3 expression, and increased the levels of IL-4. Treatment with CWP decreased apoptosis by enhancing the phosphorylation of AKT and IκB-α as well as T-cell and B-cell distribution in the spleen and thymus. Conclusions: Our findings suggest the beneficial effects of CWP supplementation during diabetes on decreasing and orchestrating the redox status and subsequently rescuing the immune cells from exhaustion.

Camel whey protein improves oxidative stress and histopathological alterations in lymphoid organs through Bcl-XL/Bax expression in a streptozotocin-induced type 1 diabetic mouse model

Type I diabetes (T1D) is a characterized by the inflammation of pancreatic islets and destruction of β cells. Long and persistent uncontrolled diabetes tends to degenerate the immune system and increase the incidence of infections in diabetic individuals. Most serious diabetic complications are mediated by the free radicals, which damage multiple cellular components through direct effects of the cell cycle regulatory proteins. Camel whey protein (CWP) has antioxidant activity and decreases the effects of free radicals. However, the effects of CWP on lymphoid organs have not been studied in the context of diabetes. Therefore, the present study was designed to investigate the dietary influence of CWP supplementation on the lymphoid organs in streptozotocin (STZ)-induced type 1 diabetic mouse model. Three experimental groups were used: non diabetic control mice, diabetic mice, and diabetic mice treated with CWP. Induction of diabetes was associated with a marked reduction in glutathione (GSH) levels; decreased activities of GSH peroxidase (GSH Px), manganese superoxide dismutase (MnSOD) and catalase; increased reactive oxygen species (ROS) levels and iNOS activity in plasma and lymphoid organs. Furthermore, diabetic mice exhibited alterations in the expression of Bax and Bcl-XL, and subsequently pathological alterations in the architecture of the bone marrow, pancreas, thymus, and spleen. Interestingly, treatment of diabetic mice with CWP robustly restored glucose, insulin, GSH, and ROS levels and the activities of GSH Px, MnSOD, catalase and iNOS. Additionally, supplementation of diabetic mice with CWP improvement in the architecture of lymphoid tissues and rescued from apoptosis through direct effects on the Bax and Bcl-XL proteins. These data revealed the therapeutic potential of CWP against diabetic complications mediated damages of lymphoid organs.

Review of Pathophysiological Aspects and Risk Factors for Liver Dysfunction

The liver is accountable for many critical functions within the body and loss of those functions can cause significant damage to the body. Liver disease is a extensive term that covers all aspects that cause the liver to fail to perform its proper functions.