Main features of the oxidative metabolism in gills and liver of Odontesthes nigricans Richardson (Pisces, Atherinopsidae)

The aim of this work was to study comparatively the oxidative metabolism in gills and liver of a silverside, Odontesthes nigricans, in their natural environment, the Beagle Channel. Oxidative damage to lipids was evaluated by assessing TBARS and lipid radical content, in gills and liver. Gills showed a significantly higher degree of damage than liver. The content of α-tocopherol, β-carotene and catalase activity showed significantly higher values in the liver than in the gills. The ascorbyl radical (A^•) content showed no significant differences between gills and liver. The ascorbate (AH⁻) content was 12 ± 2 and 159 ± 28 nmol/mg FW in gills and liver, respectively. Oxidative metabolism at the hydrophilic level was assessed as the ratio A^•/AH⁻. The ratio A^•/AH⁻ was significantly different between organs, (6 ± 2)10^− 5 and (5 ± 2)10^− 6, for the gills and the liver, respectively. Both, lipid radical content/α-tocopherol content and lipid radical content/β-carotene content ratios were significantly higher in gills as compared to the values recorded for the liver, suggesting an increased situation of oxidative stress condition in the lipid phase of the gills. Taken as a whole, the O. nigricans liver exhibited a better control of oxidative damage than the gills, allowing minimization of intracellular damage when exposed to environmental stressing conditions.     

The use of pentoxifylline as adjuvant therapy with praziquantel downregulates profibrogenic cytokines, collagen deposition and oxidative stress in experimental schistosomiasis mansoni

This study investigates the possible use of pentoxifylline (PTX), with antifibrotic and anti-inflammatory properties, as adjuvant in treatment of schistosomal liver fibrosis through determination of some profibrogenic cytokines, oxidative stress and collagen deposition. Animals were classified into seven groups: normal control (i), Schistosoma mansoni-infected untreated (ii), infected treated with praziquantel (PZQ) curative, 1000 mg/kg (iii) or sub curative, 200 mg/kg dose (iv), infected treated with PTX alone (10 mg/kg/day; 5 days/wk) for 8 weeks starting from the 2nd to the 10th week post infection (v), or in addition to curative (vi) or sub curative dose of PZQ (vii). Serum transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), matrix metalloproteinases-2 (MMP-2) and hepatic hydroxyproline (Hyp) content, glutathione related antioxidant enzymes and malondialdehyde (MDA) were determined. Results showed that S. mansoni infection produced remarkable elevations in the serum levels of TGF-β1, TNF-α, MMP-2 and the hepatic contents of Hyp, glutathione reductase (GR), MDA with significant reduction in reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) when compared with their corresponding normal controls. Treatment of infected mice with PTX in addition to PZQ curative rather than its sub curative dose produced the best results evidenced by complete normalization in the previously mentioned serum and hepatic parameters. Conclusion: PTX could attenuate liver fibrosis in early stages of S. mansoni infection through downregulation of profibrogenic cytokines, oxidative stress and collagen deposition.     

Relationship between glutathione S-transferase, catalase, oxygen consumption, lipid peroxidation and oxidative stress in eggs and larvae of Boophilus microplus (Acarina: Ixodidae)

Glutathione S-transferases (GSTs) are enzymes that act in excretion of physiologic and xenobiotic substances, protecting cells against chemical toxicity and stress. In this work, we characterized the enzymatic activity of GST in eggs and larvae of cattle tick Boophilus microplus, on different days after oviposition and eclosion. The results showed that the GST activity varied depending on the time elapsed after oviposition and eclosion. Molecules involved in mechanism of protection from oxidative stress are correlated with the increase in GST activity. The oxygen consumption kinetics showed a positive correlation with the increase in GST activity during embryogenesis. A high content of thiobarbituric acid reactive substances were observed in egg and larva extracts, indicating that ticks face high oxidative stress during embryogenesis and aging. In eggs and larvae, GST activity can be correlated to kinetic parameters of oxidative stress such as catalase and glutathione. In addition, GST activity showed strong positive correlation with lipid peroxidation, an indication that it plays a role in oxidant defences in eggs.     

Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver

Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on expression/activity of the main DDS phase-II-metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.     

Green tea (Camellia sinesis) ameliorates female Schistosoma mansoni-induced changes in the liver of Balb/C mice

This study was designed to assess the effect of green tea, an aqueous extract of Camellia sinensis, on the oxidative stress, antioxidant defense system and liver pathology of Schistosoma mansoni-infected mice. Green tea at concentration of 3% (w/v) was given orally to treated mice as sole source of drinking water from the end of the 4th week to the end of 10th week post-infection; untreated mice were allowed to drink normal water. The data of the studied S. mansoni-infected mice exhibited a suppression of hepatic total antioxidant capacity, superoxide dismutase (SOD), catalase (CAT) activity and glutathione content. The liver lipid peroxidation was deleteriously elevated in S. mansoni-infected mice. The hepatic total protein content, AST and ALT activities were profoundly decreased in the S. mansoni-infected mice. Most hepatocytes were damaged and showed abnormal microscopic appearance with aggressive necrosis. Both total protein and glycogen levels have been greatly reduced as indicated by histochemical examination. The treatment of S. mansoni-infected mice with green tea succeeded to suppress oxidative stress by decreasing the lipid peroxides but failed to significantly enhance the antioxidant defense system and deteriorated changes owing to liver damage and necrosis. In consistence with biochemical data, histopathological and histochemical data indicated that treatment of S. mansoni-infected mice with green tea could ameliorate hepatocytes thus reduce cellular necrosis and partially restore both total protein and glycogen levels. Thus, the study concluded that the green tea suppresses the oxidative stress through its constituent with free radicals scavenging properties rather than through the endogenous antioxidant defense system.     

The effect of seasonality on oxidative metabolism in Nacella (Patinigera) magellanica

We studied the seasonal variation on aerobic metabolism and the response of oxidative stress parameters in the digestive glands of the subpolar limpet Nacella (P.) magellanica. Sampling was carried out from July (winter) 2002 to July 2003 in Beagle Channel, Tierra del Fuego, Argentina. Whole animal respiration rates increased in early spring as the animals spawned and remained elevated throughout summer and fall (winter: 0.09 ± 0.02 μmol O₂ h^− 1 g^− 1; summer: 0.31 ± 0.06 μmol O₂ h^− 1 g^− 1). Oxidative stress was assessed at the hydrophilic level as the ascorbyl radical content / ascorbate content ratio (A / AH⁻). The A / AH⁻ ratio showed minimum values in winter (3.7 ± 0.2 10^− 5 AU) and increased in summer (18 ± 5 10^− 5 AU). A similar pattern was observed for lipid radical content (122 ± 29 pmol mg^− 1 fresh mass [FW] in winter and 314 ± 45 pmol mg^− 1 FW in summer), iron content (0.99 ± 0.07 and 2.7 ± 0.6 nmol mg^− 1 FW in winter and summer, respectively) and catalase activity (2.9 ± 0.2 and 7 ± 1 U mg^− 1 FW in winter and summer, respectively). Since nitrogen derived radicals are thought to be critically involved in oxidative metabolism in cells, nitric oxide content was measured and a significant difference in the content of the Fe–MGD–NO adduct in digestive glands from winter and summer animals was observed. Together, the data indicate that both oxygen and nitrogen radical generation rates in N. (P.) magellanica are strongly dependent on season.     

Hepatotoxicity potential of Saw Palmetto (Serenoa repens) in rats

Saw palmetto (Serenoa repens L.) is an herbal drug used to treat symptoms of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). There has been a report that a preparation containing this herb has caused cholestatic hepatitis in one person and some indications exist that it may have the potential to produce liver toxicity. The purpose of this study was to evaluate the effect of saw palmetto on rat liver function by measuring its effects on several enzymes and formation of malondialdehyde (MDA), a byproduct of lipid peroxidation. A significant increase in these parameters is considered an indication of liver toxicity. Thirty-six rats were divided into 6 groups of 6 animals each. They were treated for 2 or 4 weeks with a placebo or saw palmetto at doses of 9.14 or 22.86 mg/kg/body wt./day; that is, 2 x and 5 x the maximum recommended daily human dosages. After 2 or 4 weeks, the animals were sacrificed and blood was collected to prepare serum for enzyme assays, which were performed using commercially available kits. A portion of the liver was removed, and a homogenate prepared for the lipid peroxidation assay. Results showed no significant difference in animal body weight, enzyme activity, or MDA formation at either time or dosage level, as compared to controls. The data indicate that at the doses and time periods tested, saw palmetto did not produce any significant effect on the normal biological markers of liver toxicity.     

单核细胞增多性李斯特菌OpuCA蛋白介导抗氧化应激和宿主感染研究

【目的】本文旨在研究opuCA基因在单核细胞增多性李斯特菌(单增李斯特菌)生长过程及渗透胁迫下发挥的作用,探究opuCA基因参与细菌抗氧化应激和致病力的生物学功能,为阐明OpuCA蛋白介导细菌环境适应和宿主内感染的机制奠定基础。【方法】利用细菌同源重组方法获得opuCA缺失株及回补株后,通过分子生物学、感染生物学和激光共聚焦技术,研究野生株和突变株的生长能力、抗渗透应激能力、抗氧化应激能力、细胞粘附、侵袭以及胞内增殖能力。【结果】缺失opuCA基因后,李斯特菌体外生长能力并没有受到影响,但在渗透条件下生长能力减弱;opuCA缺失株在铜离子和镉离子中抗氧化应激能力降低,但在巯基特异性氧化剂肼应激中无明显变化;opuCA缺失株在细胞中的侵袭能力显著减弱,且缺失该基因导致细菌聚合actin能力下降,进而影响了细菌在胞间迁移。【结论】本研究首次证实了缺失opuCA基因能降低单增李斯特菌抗氧化应激能力和感染宿主能力,并且在渗透胁迫下细菌生长能力减弱,但具体的分子机制有待深入研究。本研究有助于深入理解单增李斯特菌OpuCA蛋白介导的细菌体外环境适应及宿主内感染的分子机制,为防控单增李斯特菌感染提供...     

Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon tetrachloride-induced acute rat liver injury

Oxidative stress is involved in the pathogenesis of chemically mediated liver injury. Since glycosaminoglycans possess antioxidant activity, the aim of this work was to assess the protective effects of hyaluronic acid and chondroitin-4-sulphate treatment in a model of carbon tetrachloride-induced liver injury. Liver damage was induced in male rats by an intraperitoneal injection of carbon tetrachloride (1 ml/kg in vegetal oil). Serum alanine aminotransferase and aspartate aminotransferase, hepatic malondialdehyde, plasma TNF-alpha, hepatic reduced glutathione and catalase, and myeloperoxidase, an index of polymorphonuclear infiltration in the jeopardised hepatic tissue, were evaluated 24 h after carbon tetrachloride administration. Carbon tetrachloride produced a marked increase in serum alanine aminotransferase and aspartate aminotransferase activities, primed lipid peroxidation, enhanced plasma TNF-alpha levels, induced a severe depletion of reduced glutathione and catalase, and promoted neutrophil accumulation. Intraperitoneal treatment of rats with hyaluronic acid (25 mg/kg) or chondroitin-4-sulphate (25 mg/kg) failed to exert any effect in the considered parameter, while the combination treatment with both glycosaminoglycans (12,5 + 12,5 mg/kg) decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, inhibited lipid peroxidation by reducing hepatic malondialdehyde, reduced plasma TNF-alpha, restored the endogenous antioxidants, and finally decreased myeloperoxidase activity. These results suggest that hyaluronic acid and chondroitin-4-sulphate possess a different antioxidant mechanism and consequently the combined administration of both glycosaminoglycans exerts a synergistic effect with respect to the single treatment.     

Schistosoma japonicum: treatment of different developmental stages in mice with long-acting praziquantel implants

This paper reports the effective treatment of Schistosoma japonicum in a mouse model with long-acting praziquantel (PZQ)-loaded poly(ε-caprolactone) implants. The implants yielded stable, high plasma PZQ concentrations ranging 100–1600 ng/mL during the 40-day investigation period. For assessment of efficacy, the implants were implanted into mice immediately after infection and at 1, 2, 3 and 4 weeks after infection to treat the schistosomes at different developmental stages. All the mice were sacrificed at 6 weeks after infection for worm and egg recovery, worm morphology examination, and histopathological analysis of implantation site tissues. The worm burdens, egg burdens, and numbers of miracidia hatched from the retrieved eggs for all the implant-treated groups (except groups T2-A, T4 and T5) were reduced by 100% when compared with the control group. From groups T2-A, T4 and T5, some schistosome debris was recovered. Eggs were found in only group T5 for which the time between infection and implantation was 4 weeks, which enabled the maturation of juvenile female schistosomes into adult ones that lay eggs. Histopathological observations of implantation tissue showed no evidence of granulomatous foreign-body or lymphoid cell aggregation, demonstrating good biocompatibility of the PZQ implants. These results demonstrate that the long-acting PZQ implants can kill schistosomes at any developmental stages and attenuate/avoid the associated liver damage.     

Involvement of oxidative stress and role of antioxidative defense system in growing rice seedlings exposed to toxic concentrations of aluminum

When seedlings of rice (Oryza sativa L.) cultivar Pant-12 were raised in sand cultures containing 80 and 160 μM Al³⁺ in the medium for 5–20 days, a regular increase in Al³⁺ uptake with a concomitant decrease in the length of roots as well as shoots was observed. Al³⁺ treatment of 160 μM resulted in increased generation of superoxide anion (O₂ ⁻) and hydrogen peroxide (H₂O₂), elevated amount of malondialdehyde, soluble protein and oxidized glutathione and decline in the concentrations of thiols (-SH) and ascorbic acid. Among antioxidative enzymes, activities of superoxide dismutase (SOD EC 1.15.1.1), guaiacol peroxidase (Guaiacol POX EC 1.11.1.7), ascorbate peroxidase (APX EC 1.11.1.11), monodehydroascorbate reductase (MDHAR EC 1.6.5.4), dehydroascorbate reductase (EC 1.8.5.1) and glutathione reductase (EC 1.6.4.2) increased significantly, whereas the activities of catalase (EC EC 1.11.1.6) and chloroplastic APX declined in 160 μM Al³⁺ stressed seedlings as compared to control seedlings. The results suggest that Al³⁺ toxicity is associated with induction of oxidative stress in rice plants and among antioxidative enzymes SOD, Guaiacol POX and cytosolic APX appear to serve as important components of an antioxidative defense mechanism under Al³⁺ toxicity. PAGE analysis confirmed the increased activity as well as appearance of new isoenzymes of APX in Al³⁺ stressed seedlings. Immunoblot analysis revealed that changes in the activities of APX are due to changes in the amounts of enzyme protein. Similar findings were obtained when the experiments were repeated using another popular rice cv. Malviya-36.     

Iron increases liver injury through oxidative/nitrative stress in diabetic rats: Involvement of nitrotyrosination of glucokinase

Excessive tissue iron levels are associated with the increase of oxidative/nitrative stress which contributes to tissue damage that may elevate the risk of diabetes. Therefore, we investigated the effects of iron on diabetes-associated liver injury and whether iron-related tyrosine nitration participated in this process. Rats were randomly divided into four groups: control, iron overload (300 mg/kg iron dextran, i.p.), diabetic (35 mg/kg of streptozotocin i.p. after administration of a high-fat diet) and diabetic simultaneously treated with iron. Iron supplement markedly increased diabetes-mediated liver damage and hepatic dysfunction by increasing liver/body weight ratio, serum levels of aspartate and alanine aminotransferase, and histological examination, which were correlated with elevated levels of lipid peroxidation, protein carbonyls and tyrosine nitration, oxidative metabolism of nitric oxide, and reduced antioxidant capacity. Consequently, the extent of oxidized/nitrated glucokinase was markedly increased in the iron-treated diabetic rats that contribute to a decrease in its expression and activity. Further studies revealed a significant contribution of iron-induced specific glucokinase nitration sites to its inactivation. In conclusion, iron facilitates diabetes-mediated elevation of oxidative/nitrative stress, simultaneously impairs liver GK, and can be a link between enzymatic changes and hepatic dysfunction. These findings may provide new insight on the role of iron in the pathogenesis of diabetes mellitus.     

Leishmania amazonensis META2 protein confers protection against heat shock and oxidative stress

The META cluster of Leishmania amazonensis contains both META1 and META2 genes, which are upregulated in metacyclic promastigotes and encode proteins containing the META domain. Previous studies defined META2 as a 48.0-kDa protein, which is conserved in other Leishmania species and in Trypanosoma brucei. In this work, we demonstrate that META2 protein expression is regulated during the Leishmania life cycle but constitutive in T. brucei. META2 protein is present in the cytoplasm and flagellum of L. amazonensis promastigotes. Leishmania META2-null replacement mutants are more sensitive to oxidative stress and, upon heat shock, assume rounded morphology with shortened flagella. The increased susceptibility of null parasites to heat shock is reversed by extra-chromosomal expression of the META2 gene. Defective Leishmania promastigotes exhibit decreased ability to survive in macrophages. By contrast, META2 expression is decreased by 80% in RNAi-induced T. brucei bloodstream forms with no measurable effect on survival or resistance to heat shock.     

Modulation of radiation-induced biochemical alterations in mice by rosemary (Rosemarinus officinalis) extract

Radioprotective effect of leaves extract of Rosemarinus officinalis (ROE) has been studied against 6 Gy gamma-radiations in the liver of Swiss albino mice at various post-irradiation intervals between 12 h and 30 days. In control animals (without ROE treated irradiated), an elevation in glycogen, protein, acid and alkaline contents was found till day 5th, but thereafter decreased at successive intervals without returning to normal. Cholesterol level was found to be lower than normal till 10th day, then increased up to 20th day but later declined without restoring normal level. A similar trend of variation in these biochemical parameters was observed in experimental group (ROE pretreated irradiated) also but to a lower extent. ROE significantly delayed and inhibited the rise in these biochemical parameters. Almost normal values of such constituents were regained by day 30th in experimental animals; whereas in control animals, normal values were not ever attained. In control animals, there was an elevation in lipid peroxidation (LPx) and a decrease in glutathione (GSH) in blood and liver; whereas in experimental group, decline in LPx accompanied by an increase in GSH concentration was observed.     

Pycnogenol prevents potassium dichromate (K2Cr2O7)-induced oxidative damage and nephrotoxicity in rats

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. Recent evidence indicates that Pycnogenol^® (PYC), French maritime pine bark extract, exhibits antioxidant potential and protects against various oxidative stressors. The aim of the present study was to examine the modulating impacts of PYC on potassium dichromate (K₂Cr₂O₇)-induced oxidative damage and nephrotoxicity in rats. Male Wistar rats were divided into four groups. The first group was control, the second group was control plus pre-treated with PYC (10 mg/kg, body weight; in saline; intraperitoneally; once daily for 3 weeks) as drug control and the third group was saline pre-treated plus treated with a single injection of K₂Cr₂O₇ (15 mg/kg, body weight; in saline; intraperitoneally) as toxicant group. The fourth group was PYC pre-treated plus K₂Cr₂O₇ injected. Forty-eight hours after K₂Cr₂O₇-treatment, blood was drawn for estimation of renal injury markers in serum. Rats were then sacrificed, and their kidneys were dissected for biochemical and histopathological assays. K₂Cr₂O₇-treated rats showed significant increases in markers of renal injury in serum, including blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), which were significantly (P < 0.05) decreased by PYC pre-treatment. Moreover, prophylactic pre-treatment of rats with PYC significantly (P < 0.05) ameliorated increased thiobarbituric reactive substances (TBARS), malonaldehyde (MDA) and protein carbonyl (PC), and decreased levels of glutathione (GSH) and catalase activity in the kidney homogenate of K₂Cr₂O₇-treated rats. These results were also supported and confirmed with histopathological findings. The study suggests that PYC is effective in preventing K₂Cr₂O₇-induced oxidative mediated nephrotoxicity, but more studies are needed to confirm the effects of PYC as a nephroprotective agent.     

Gender related differences in the oxidative stress response to PCB exposure in an endangered goodeid fish (Girardinichthys viviparus)

Polychlorinated biphenyls (PCBs) are persistent xenobiotics within aquatic environments, which elicit diverse toxic effects such as induction of oxidative stress. Despite numerous earlier studies, no detailed information exists on the toxic response by different sexes in fish. The aim of this study was to determine sex-linked differences in oxidative stress response and antioxidant defenses in Girardinichthys viviparus, an endangered fish endemic to Mexico, when exposed to sub-lethal concentrations of waterborne PCBs. The biological markers evaluated were lipid peroxidation (LPOX), superoxide dismutase (SOD) and catalase (CAT) activity. Adult eight-month-old specimens born in the laboratory were exposed to ½ of the LC₀ (0.92 mg PCBs/L) in semi-hard synthetic water and sacrificed on days 1, 2, 4, 8 and 16 for biomarker assays. Sex-linked differences were observed in the control fish with respect to all three factors assayed. PCBs elicited significant (p < 0.01) time- and sex-dependent LPOX levels which were higher in the case of males. In PCB-treated G. viviparus, SOD activity was depressed in both sexes and appears to return to pre-exposure levels after 16 days in males only. In contrast, CAT was significantly induced (p < 0.01) in both sexes. This enzyme may be responsible for balancing oxidative stress and antioxidant defenses under experimental conditions. PCBs at sub-lethal concentrations are hazardous to both sexes of G. viviparus since these compounds are able to induce liver LPOX and changes in the antioxidant defense activities. The relationship between these biomarkers and cytochrome P450 and CYP1A induction is also discussed.     

Antioxidative effects of hesperetin against 7,12-dimethylbenz(a)anthracene-induced oxidative stress in mice

We investigated the effects of the chronic administration of hesperetin on the activation of the antioxidant defence system in mice in which oxidative stress had been induced by 7,12-dimethylbenz(a)anthracene (DMBA). Mice were divided randomly into three treatment groups. Hesperetin was administered orally to two of the three groups at 10 and 50 mg/kg body weight for 5 weeks. Subsequently, each group was subdivided randomly into DMBA-treated and untreated groups. The DMBA-treated groups were intragastrically administered a dose of 34 mg/kg BW in corn oil vehicle twice a week for 2 weeks. The TBARS value showed a tendency to decrease following hesperetin treatment; these decreases were significantly greater in the DMBA-treated than the untreated groups. Hesperetin significantly decreased the carbonyl content at the high dose in both DMBA-treated and untreated mice. Catalase and SOD activity were increased by hesperetin; this increase was more pronounced in DMBA-treated than untreated mice. Catalase, Mn-SOD, and CuZn-SOD expression analyses supported these results. Although the GSH-px and GR activity were little affected, hesperetin treatment significantly increased the GSH/GSSG ratio in the DMBA-treated group in a dose-dependent manner. These results suggest that hesperetin shows antioxidant activity and plays a protective role against DMBA-induced oxidative stress.     

Schistosoma mansoni: N-acetylcysteine downregulates oxidative stress and enhances the antischistosomal activity of artemether in mice

Artemether (Art), a derivative of the antimalarial artemisinin, also exhibit antischistosomal properties. N-acetylcysteine (NAC) has a diversity of applications, largely because of the chemical properties of the thiol moiety present in its structure. The ability of this moiety to sweep reactive oxygen species is well-established with NAC. This study investigates the ability of NAC to enhance the therapeutic potential of Art against adult Schistosoma mansoni infection and evaluates the protective role of this antioxidant on S. mansoni-induced oxidative stress. Mice were divided into five groups; normal (i), infected control (ii), infected treated with NAC, 300 mg/kg 5 days a week/4weeks (iii), infected treated with Art (300 mg/kg) 7 weeks post infection (iv) and infected treated with both NAC and Art (v). Results showed that Art produced a significant reduction in total number of worms when used alone. Also, it decreased hepatic ova count significantly accompanied with an increase in the percentage of dead ova. Treatment with NAC alone increased the percentage of dead ova; meanwhile, it enhanced the decrease in total number of worms and hepatic ova count when used with Art. Infection with S. mansoni significantly increased tissue GSH, GR, SOD and serum ALT and GGT, while decreased the activities of GST, GPx and the levels of proteins and albumin compared to normal control. Treatment with NAC alone approximately recovered the contents of GSH, activities of GPx and levels of serum albumin, ALT and GGT relative to normal control. A tendency for normalization in activities of the antioxidant enzymes mentioned above and serum levels of liver function tests was observed in the groups treated with Art alone or Art + NAC. Conclusion: NAC downregulates oxidative stress induced by S. mansoni infection and enhances the therapeutic potential of artemether against adult schistosomes.