• Energy Research
• Closed Access close
• Open Source close
• Embargo close
• health sciences close
• 3. Good health close

Abstract The influence of sorbitol on the rate of oxidation of ethanol and accumulation of acetaldehyde was studied in intact rats pretreated with propyl thiouracil or triiodothyronine. Sorbital inhibited ethanol oxidation by 58 per cent in hypothyroid and by 33 per cent in euthyroid rats but no significant inhibition was observed in hyperthyroid animals. Fructose increased and sorbitol significantly decresed the acetaldehyde level of hepatic venous blood in euthyroid animals given ethanol. The experiments suggested that the higher the oxidation rate of ethanol the higher the initial concentration of acetaldehyde in the hepatic venous blood of intact rats.

To examine the combined hepatotoxic and nephrotoxic effects of cadmium and ethanol, rats maintained on an ethanol containing liquid diet (5% w/w) were given cadmium either acutely (3 x 1 mg/kg IP) or subacutely (about 14 mg/kg/day PO for 6 weeks). Parameters tested were cadmium, zinc and copper contents of blood and various organs, metallothionein (MT) contents, polysome profile of liver and kidneys, serum SDH and GPT levels and creatinine clearance. Ethanol reduced the hepatic MT contents without altering the polysome profile and the zinc and copper contents. Cadmium on the other hand raised the MT contents in liver and kidneys. This effect of cadmium predominated in the combined treatment. Morphological examination and functional tests (SDH, GPT, creatinine clearance) indicate that cadmium does not enhance the toxic effects of ethanol, and vice versa.

Nigella sativa L. (Ranunculaceae) is considered as a therapeutic plant-based medicine for liver damage. In this study, the aim was to study the effect of Nigella sativa oil (NSO) pretreatment on ethanol-induced hepatotoxicity in rats.Rats were given Nigella sativa oil at doses of 2.5 and 5.0 mL·kg(-1), orally for 3 weeks, followed by oral ethanol (EtOH) administration (5 g·kg(-1)) every 12 h three times (binge model).Binge ethanol application caused significant increases in plasma transaminase activities and hepatic triglyceride and malondialdehyde (MDA) levels. It decreased hepatic glutathione (GSH) levels, but did not change vitamins E and vitamin C levels and antioxidant enzyme activities. NSO (5.0 mL·kg(-1)) pretreatment significantly decreased plasma transaminase activities, hepatic MDA, and triglyceride levels together with amelioration in hepatic histopathological findings.NSO pretreatment may be effective in protecting oxidative stress-induced hepatotoxicity after ethanol administration.

Propolis has been used as a medicinal agent to treat infections and promote wound healing for centuries. The aim of the present study was to test the antimicrobial, antioxidant, and cytotoxic activities of a new type of Brazilian propolis, popularly called red propolis, as well as to analyze its chemical composition. The antimicrobial activity against Staphylococcus aureus ATCC 25923 and Staphylococcus mutans UA159 was evaluated and the chloroform fraction (Chlo-fr) was the most active with lower MIC ranging from 25 to 50 microg/ml. The hexane fraction (H-fr), having the highest concentration of total flavonoids, showed the best sequestrating activity for the free radical DPPH. The ethanolic extract of propolis (EEP) showed cytotoxic activity for the HeLa tumor cells with an IC(50) of 7.45 microg/ml. When the EEP was analyzed by GC-MS, seven new compounds were found, among which four were isoflavones. Our results showed that the red propolis has biologically active compounds that had never been reported in other types of Brazilian propolis.

Diseases related to ethanol abuse, especially binge drinking, are becoming one of the most costly health problems in the world. Ethanol-induced DNA damage plays a key role in the etiology of these diseases. New compounds are expected to offer new options against ethanol-induced genotoxicity. It was found, for the first time, that resveratrol and three analogues with 3,5-dimethoxyl groups in the A-ring, such as (E)-4-(3,5-dimethoxystyryl)phenol (RV32), or with a quinolyl in the B-ring, such as (E)-5-[2-(quinolin-4-yl)vinyl]benzene-1,3-diol (RV01) and (E)-4-(3,5-dimethoxystyryl)quinoline (RV02), strongly inhibited ethanol-induced oxidative DNA damage in human peripheral lymphocytes in vitro. Resveratrol and RV32 with more hydroxyl groups in structures showed stronger direct scavenging activity of hydroxyl radicals than RV01 and RV02. Moreover, all compounds reduced hydroxyl radical generation by regulating the mRNA expression of alcohol dehydrogenase 1B and acetaldehyde dehydrogenase 2. Further studies proved resveratrol and three analogues activated the base excision repair system in transcriptional and protein levels in DNA repair process. Both 3,5-dimethoxyl groups and quinolyl modification may enhance such activity. In summary, resveratrol and its three analogues revealed significant protective activity against ethanol-induced oxidative DNA damage in human peripheral lymphocytes, which demonstrates their potential for use in prevention and treatment of the diseases related to ethanol abuse.

Individual and racial differences in response to alcohol and with respect to alcoholism have strong genetic predispositions. Most studies on the actual genetic determinants have concentrated on the isozymes of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), the two enzymes of the primary pathway of alcohol metabolism. Although few "activity" variants (associated with mutations in the structural genes) of the two enzymes are known to exist in susceptible groups, these observations do not offer an adequate explanation for the observed variability in response to alcohols in the population. Some recent studies have reported alterations in the specific activity of the two enzymes following exposure to alcohol for different lengths of time in man, rat, and mice. The induction–repression so observed is hypothesized to be regulated by one or more inducibility genetic elements (IGE) associated with the structural loci of the two enzymes. Variability in IGE will permit a genotype (individual) specific response in ADH and ALDH specific activity when challenged with a given level of alcohol. Considering the relative toxicity of acetaldehyde, the primary metabolite of this pathway, the resistant individuals would be expected to show ALDH induction. Conversely, the susceptible individuals should respond to alcohol by ALDH repression. The ability of an individual to show induction or repression following alcohol ingestion will depend on his or her IGE genotype(s) associated with specific enzyme loci. Also, the degree of polymorphism at these loci would be expected to be extensive and yet population and race specific. Once experimentally established, this approach could have important implications in screening, counselling, prevention, and in novel approaches to treatment.Key words: alcohol metabolism, acetaldehyde, alcohol dehydrogenase, aldehyde dehydrogenase, alcohol sensitivity, induction–repression of enzymes.

Uncontrolled inflammation causes health problems. Extracellular signal-regulated kinase (ERK) phosphorylates signal transducer and activator of transcription 3 (STAT3) at Ser727, resulting in inflammation. The leaf of Vernonia amygdalina (VA) is a medicinal herb for managing inflammation-associated diseases. Oral administration or topical application of VA leaf extract exerts anti-inflammatory effects in rat models. However, the anti-inflammatory mechanisms of the herb are not fully understood.In this study, we aimed to investigate the involvement of ERK/STAT3 (Ser727) signaling in the anti-inflammatory effects of an ethanolic extract of VA leaves.Extracts of VA leaves were prepared with different concentrations of ethanol. A LPS-stimulated RAW264.7 cell model was used for in vitro assays, and a TPA (12-O-tetradecanoylphorbol-13-acetate)-induced ear edema mouse model was employed for in vivo assays. The 95% ethanol extract of VA leaves (VAE) exerted the strongest inhibitory effect on nitric oxide (NO) production in LPS-stimulated macrophages; thus it was selected for use in this study. Hematoxylin and eosin (H&E) staining was used to examine pathological conditions of mouse ear tissues. Griess reagent was employed to examine NO generation in cell cultures. Immunoblotting and ELISA were used to examine protein levels, and RT-qPCR was employed to examine mRNA levels.Topical application of VAE ameliorated mouse ear edema induced by TPA. VAE suppressed the phosphorylation of ERK (Thr202/Tyr204) and STAT3 (Ser727); and decreased protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in the mouse ear tissues and in LPS-stimulated RAW 264.7 cells. VAE also inhibited NO production, and lowered mRNA levels of IL-6, IL-1β and TNF-α in the macrophages.VAE ameliorates TPA-induced mouse ear edema. Suppression of ERK/STAT3 (Ser727) signaling is involved in VAE's anti-inflammatory effects. These novel data provide further pharmacological justifications for the medicinal use of VA in treating inflammation-associated diseases, and lay the groundwork for developing VAE into a new anti-inflammatory agent.

Incubation of lysozyme with acetaldehyde (0.44 M) at room temperature for 2 h produces a 62% inhibition of enzymic activity. Because the active site cleft contains tryptophyls, asparagine, glutamine, and an arginine residue, and because acetaldehyde reacts with indoles, amides, and guanidines, it is suggested that these sites are likely ones for alkylation. The epsilon-amino groups of lysines on the surface of the molecule are also susceptible to covalent modification. Total acetylation of lysozyme has been reported to inactivate the enzyme. These results suggest the possibility that inactivation of a fraction of the lysozyme activity by acetaldehyde may decrease the effectiveness of the enzyme in chronic alcoholics, thereby leading to an increased potential for susceptibility to bacterial infection.