BackgroundThe resistance to chemotherapy is a major obstacle in the treatment of hepatocellular carcinoma (HCC), necessitating the discovery of additional agents. The use of natural products in this respect is extensively under investigation. Methods Two hundred and ten male albino rats were used, divided into 14 groups. Selected groups were pre-treated with vitamin C (ascorbic acid, AA) and/or diallyl sulphide (DAS). Hepatocellular dysplasia was initiated by a single intra-peritoneal (IP) injection of diethyl nitrosamine (DENA), diabetes was induced by a single IP injection of Streptozotocin (STZ). Other groups were treated with cisplatin (CP) alone or combined with AA and/or DAS for 14 weeks. This work aims to check if naturally occurring materials can help in improving response to CP chemotherapy using ploylol profile as a new index in management of HCC. ResultsThe results revealed that DENA significantly increased relative liver weight, serum ALT, AST and GGT activities, AFP, TNF-α and IL-6 levels, expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and Bcl2 proteins in the liver with decrease in body weight, expression of Bax protein and Bax/Bcl2 ratio in the liver. These effects were more pronounced in DENA+STZ group. These parameters showed relative correlation to AFP levels in HCC, in response to AA and/or DAS treatment except for SDH. Treatment with CP and/or AA and/or DAS significantly modulated most of these parameters except for SDH which showed no significant change in response to the suggested treatment. ConclusionsIn conclusion, AA and/or DAS showed apparent chemo-sensitizing, anti-inflammatory, AR inhibitory, apoptotic inducing and anti-diabetic activities, indicating new aspects for use as adjuvant to chemotherapy. Induction of diabetes in hepatocellular dysplasia -bearing rats showed higher resistance to chemotherapy. Ploylol profile is a useful prognostic tool in HCC patients with diabetic interference.

Hydrogen sulfide (H2S) is a gaseous mediator recognized as important neuromodulator agent in the central nervous system. Since stress is among the most important factors involved in several pathophysiological brain processes. This study aim to investigate the effect of exogenous H2S on the possible negative effect of stress on the brain of rats and the underlying mechanisms. Rats were divided into 3 groups: control, stressed, H2S treated + stress. Brain injury markers measured were serum S100 protein and gamma enolase. Stress leads to obvious detrimental effects on the brain tissues; it produced significant increase in serum level of the above mentioned brain injury markers, and significant increase in brain levels of nitric oxide (NO), tumor necrosis factor-alpha (TNFα), and malondialdehyde (MDA) the lipid peroxidation degradative product along with significant decrease in brain glutathione level. H2S pre-treatment before stress application abolished the above detrimental effects of stress on the brain tissue since it produced significant decreases in the stressinduced expression of brain injury markers, brain TNFα, brain NO and brain MDA, and significant increases in the stress-induced reduction of brain glutathione. H2S has significant neuroprotective role in the nervous system against stress-induced significant brain injury through its antioxidant and anti-inflammatory effects.

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Background: Diabetic myopathy is a common complication of diabetes mellitus (DM), yet experimental studies concentrated on insulin deficiency and motor neuropathy as the cause. C-peptide deficiency has recently been implicated in the pathogenesis of diabetic neuropathy. However, its effects on the contractile properties of skeletal muscles need investigation.Objective: Testing the gastrocnemius muscle response to electric stimulation in normal and type II diabetic adult male albino rats with and without treatment by C-peptide or nitric oxide modulators and correlating it with the metabolic error.Material and methods: Thirty six adult male albino rats of a local strain and average weight (160-170g) were equally divided into the following groups: 1-Control group (C): normal non diabetic rats kept on normal pellet diet (NPD) without any treatment, Diabetic groups; Type II diabetes was induced by high fat diet (HFD), followed after 2 weeks by a single intraperitoneal injection of low dose streptozotocin (STZ) to induce partial pancreatic β-cell damage. One week after STZ injection, diabetes was verified by high serum glucose level (≥ 200 mg/dl), and diabetic rats were further classified into the following groups according to subsequent treatment; 2-Diabetic control (no further treatment), 3-Diabetic+C-peptide, 4-Diabetic+ N G -L-Arginine Methyl Ester (L-NAME); a nitric oxide synthase (NOS) inhibitor, 5-Diabetic+C-peptide+L-NAME, and 6-Diabetic+L-arginine; the substrate of NOS. Treatment continued for 4 weeks, during which rats were maintained on normal or HFD according to group. Under urethane anesthesia, the right gastrocnemius was exposed, subjected to direct electric stimulation with maximal low frequency stimulation. The peak force and the time till 50% fatigue (1/2 the peak force) were determined. The left gastrocnemius served as resting muscle. The experiment was then terminated by stopping stimulation and, immediately, rats were decapitated, blood samples were collected, and both gastrocnemius muscles were excised from origin to insertion and the liver was taken. Tissue and serum samples were subjected to biochemical analysis.Results: HFD and STZ injection induced the metabolic error of type II diabetes in rats with diabetic myopathy picture characterized by significant lowering of peak muscle force, muscle weight, muscle and liver glycogen with a significant shortening of the time till 50% fatigue. The generalized metabolic error was manifested by hyperglycemia, hypoinsulinemia, increased insulin resistance indicated by a higher homeostatic model of insulin resistance (HOMA-IR), and dyslipidemia with higher atherogenic index. Oxidative stress was manifested by a significantly high malodialdehyde (MDA) and nitric oxide was significantly lowered. These errors were corrected with C-peptide treatment, but its beneficial effects were partially antagonized by L-NAME combination. L-arginine treatment partially corrected, while L-NAME treatment alone worsened the error. Conclusion:Metabolic and functional deteriorati...