Andraš Š. Štajn

Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: protective role of coenzyme Q10 and Vitamin E.

The aim of this study was to investigate the protective role of coenzyme Q(10) (CoQ(10), 20mg/kg) and Vitamin E (Vit E, 20 IU/kg) alone or in combination against cadmium (Cd, 0.4 mg/kg) induced lipid peroxidation and changes in antioxidant defense system in the rat testes. The obtained results showed that Cd increased lipid peroxidation in the testes, suggesting that Cd-induced oxidative stress, while CoQ(10) and Vit E treatment reversed this change to control values. Acute intoxication with Cd was followed by significantly decreased activity of antioxidant enzymes (SOD, CAT, GSH-Px, GR and GST). Vitamins C and E concentrations also significantly declined in Cd-exposed rat testes. Treatment with CoQ(10) and Vit E reversed Cd-induced alterations of antioxidant defense system and significantly prevented Cd-induced testes damage. These results suggest that both CoQ(10) and Vit E function as a potent antioxidant in protection of rats testes against the oxidative stress induced by Cd.

Effect of Cadmium and Selenium on the Antioxidant Defense System in Rat Kidneys

To examine effects of exogenous Cd on the kidney antioxidant defense system (AOS) and the possible protective role of Se against Cd toxicity, male Wistar albino rats (2 months old) were exposed during 30 days to oral intake of 200 ppm Cd (as CdCl2), 0.l ppm Se (as Na-selenite) or to the same doses of Cd / Se, simultaneously. Marked accumulation of Cd (23.44 +/- 0.69 micrograms/g w.m.) and marked alterations of AOS, resulting in kidney injury (renal pseudohypertrophy), were found in Cd-treated rats. Activities of total superoxide dismutase (SOC, EC 1.15.1.1), manganese-containing superoxide dismutase (MnSOD) and selenium-dependent glutathione peroxidase (Se GSH-Px, EG 1.11.1.9) were significantly reduced, whereas that of glutathione-S-transferase (CST, EC 2.5.1.18) and vitamin E (vit E) concentration were significantly increased in the kidneys of Cd-treated rats. Kidney catalase (CAT, EC 1.11.1.6) activity, ascorbic acid (AsA) and red blood cell glutathione (GSH, GSSG) levels were not markedly influenced by CD uptake. In kidneys of Se treated rats, the activities of total SOD, copper-zinc-containing superoxide dismutase (CuZnSOD) and GST were significantly increased Activities of kidney CAT and Se GSH-Px were largely unchanged, whereas significant increases of the kidney AsA and vit E concentrations occurred. In Cd + Se-cotreated rats, the kidney activities of MnSOD, CAT and Se GSH-Px, as well as vit E concentration, were the same as in controls, whereas CuZnSOD and GST activities and concentration of AsA exceeded normal values. These data indicate that Se only partially improves the AOS that is insufficient to prevent Cd-induced nephrotoxicity.

Lipid Peroxidative Damage on Cisplatin Exposure and Alterations in Antioxidant Defense System in Rat Kidneys: A Possible Protective Effect of Selenium

Cisplatin (Cis-diamminedichloroplatinum II, CP) is an important chemotherapeutic agent, useful in the treatment of several cancers, but with several side effects such as nephrotoxicity. The present study investigated the possible protective effect of selenium (Se) against CP-induced oxidative stress in the rat kidneys. Male Wistar albino rats were injected with a single dose of cisplatin (7 mg CP/kg b.m., i.p.) and selenium (6 mg Se/kg b.m, as Na2SeO3, i.p.), alone or in combination. The obtained results showed that CP increased lipid peroxidation (LPO) and decreased reduced glutathione (GSH) concentrations, suggesting the CP-induced oxidative stress, while Se treatment reversed this change to control values. Acute intoxication of rats with CP was followed by statistically significant decreased activity of antioxidant defense enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST). Treatment with Se reversed CP-induced alterations of antioxidant defense enzyme activities and significantly prevented the CP-induced kidney damage.

Oxidative stress and changes in antioxidative defense system in erythrocytes of preeclampsia in women.

The present study was designed to investigate whether oxidative stress occurred to erythrocytes in preeclampsia and was related to disease. Indicative markers of oxidative stress and changes in antioxidant defense system were assayed in the erythrocytes of 22 healthy pregnant and 20 women with preeclampsia. Results of our work indicated high concentration of hydrogen peroxide, nitrite, peroxynitrite and lipid peroxides in preeclampsia compared to healthy pregnant women. Concentration of superoxide anion was lower in preeclamptic women. There were no differences in concentrations of vitamin E, reduced glutathione and oxidized glutathione. Activity of glutathione-S-transferase (GST) was higher while activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were lower in preeclamptic women. There were no differences in glutathione peroxidase (GSH-Px) activity between the two investigated groups. These results suggest that preeclampsia was characterized by oxidative stress and alteration of antioxidative defense system by disbalance in oxidative/antioxidative status of erythrocytes.

Combined effects of coenzyme Q10 and Vitamin E in cadmium induced alterations of antioxidant defense system in the rat heart

Our study investigated the possible protective effects of coenzyme Q(10) (CoQ(10)) and Vitamin E (Vit E) alone or in combination against cadmium (Cd) induced alterations of antioxidant defense system in the rat heart. Male Wistar rats were injected with a single dose of CdCl(2) (0.4mg Cd/kg BW i.p.), CoQ(10) (20mg CoQ(10)/kg BW i.m.) and Vit E (20IU Vit E/kg BW i.m.), alone or in combination. Acute intoxication of rats with Cd were followed by significantly increased activity of antioxidant defense enzymes (CuZn SOD, GSH-Px, GST and GR), while the activity of Mn SOD was decreased in the heart. The treatment with Cd significantly decreased Vit C and Vit E concentrations. Treatment with CoQ(10) and Vit E reversed Cd-induced alterations of antioxidant defense system. The obtained results support the assumption that CoQ(10) and Vit E functions cooperatively with endogenous antioxidants and diminished toxic effects of Cd in rat heart.

Protective effects of oestradiol against cadmium-induced changes in blood parameters and oxidative damage in rats

Summary The aim of this study was to investigate the protective effects of oestradiol (E2, 4 mg kg-1 b.w. i.p.) against cadmium-induced (Cd, 2 mg kg-1 b.w. i.p.) blood changes in rats. Cadmium induced a significant decline in haemoglobin, haematocrit, and total erythrocyte, lymphocyte, and thrombocyte count, whereas total leukocytes and granulocytes increased. A significant increase was also observed in serum cholesterol, triglycerides, glucose, AST, and ALT activities, whereas total protein and albumin levels dropped significantly. Administration of E2 in combination with Cd alleviated most of these adverse effects. In terms of oxidative stress, Cd significantly increased oxygen-free radicals (O2 •- and H2O2) in neutrophils and lipid peroxidation in erythrocytes, whereas E2 treatment reversed these changes to control values. Acute Cd poisoning significantly lowered antioxidant enzyme (SOD and CAT) activity and the level of non-enzymatic antioxidants (GSH and vitamin E), while increasing in GSSG. Treatments with E2 reversed Cd-induced effects on the antioxidant defences and significantly lowered Cd-induced oxidative damage in erythrocytes. This study suggests that exogenous E2 effectively restores redox balance in rat erythrocytes and counters adverse haematological and biochemical effects of Cd poisoning. It also improves the antioxidant capacity of erythrocytes, acting in synergy with endogenous antioxidants. Sažetak Cilj ovog istraživanja bio je ispitati moguće zaštitne učinke estradiola (E2, 4 mg kg-1 tjelesne težine i.p.) protiv kadmijem izazvanih (Cd, 2 mg kg-1 tjelesne težine i.p.) promjena u krvi štakora. Kadmij je značajno smanjio vrijednosti hemoglobina, hematokrita, eritrocita, limfocita i trombocita te povećao vrijednosti ukupnih leukocita i granulocita. Također je uočen značajan rast razina AST i ALT, serumskog kolesterola, triglicerida i glukoze te pad razina ukupnih proteina i albumina. Primjena E2 u kombinaciji s Cd ublažila je većinu tih štetnih učinaka Cd. U pogledu oksidacijskog stresa, Cd je značajno potaknuo ne samo nastanak slobodnih kisikovih radikala (O2 •- i H2O2) u neutrofilima nego i lipidnu peroksidaciju u eritrocitima, a primjena E2 te je promjene svela na kontrolne vrijednosti. Akutno otrovanje kadmijem osjetno je smanjilo aktivnost antioksidativnih enzima SOD i CAT te razinu neenzimskih antioksidansa GSH i vitamina E, a povećalo razinu GSSG. Primjena E2 preokrenula je promjene u sustavu antioksidacijske obrane i značajno spriječila oksidacijska oštećenja u eritrocitima izazvana kadmijem. Prema rezultatima ovog istraživanja, E2 se učinkovito bori s disbalansom redoks statusa eritrocita i negativnim hematološkim i biokemijskim učincima nastalima nakon akutnog trovanja štakora kadmijem. Egzogeno primijenjen E2 pridonosi poboljšanju antioksidativnog kapaciteta eritrocita, djelujući sinergistički s endogenim antioksidansima.

The antioxidative effect of estradiol therapy on erythrocytes in women with preeclampsia.

In the present study, we evaluated changes of both oxidative stress marker concentrations in erythrocytes and values of blood pressure, as well as their relation during short-term estradiol therapy in preeclampsia. Serum estradiol concentrations were also recorded. The results of this study showed significant decrease of mean arterial pressure (MAP) values during estradiol therapy, whereas there was no significant change in serum estradiol concentrations. Decreased concentrations of superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), nitrite (NO(2)(-)), peroxynitrite (ONOO(-)) and lipid peroxide (LPO) were found during estradiol therapy in erythrocytes. No changes were found in the activity of gluthatione-S-transferase (GST). The decrease of MAP values was positively correlated with the reduction of concentrations of O(2)(-), H(2)O(2), NO(2)(-) and ONOO(-) in erythrocytes during estradiol therapy. The obtained results suggest that short-term intramuscular administration of estradiol shows antioxidative effects in erythrocytes and reduces blood pressure in preeclampsia.

Prooxidative effects of aspartame on antioxidant defense status in erythrocytes of rats

Since aspartame (l-aspartyl-l-phenylalanine methyl ester, ASP) is one of the most widely used artificial sweeteners, the aim of the present study was to investigate its effects on serum glucose and lipid levels as well as its effects on oxidative/antioxidative status in erythrocytes of rats. The experiment included two groups of animals: the control group was administered with water only, while the experimental group was orally administered with ASP (40 mg/kg b.w.) daily, for a period of six weeks. When compared with the control group, the group administrated with ASP indicated higher values of serum glucose, cholesterol and triglycerides. Significantly increased concentrations of superoxide anion (O2•−), hydrogen peroxide (H2O2), peroxynitrite (ОNОО−) and lipid peroxides (LPO) were recorded in the erythrocytes of ASP treated group in comparison to the control group. In the course of chronic ASP administration, the following was observed: the concentration of reduced glutathione (GSH) and the activity of catalase (CAT) increased. Thus, these findings suggest that long-term consumption of ASP leads to hyperglycemia and hyperlipidemia, as well as to oxidative stress in erythrocytes.

Protective effects of quercetin and vitamin C against nicotine-induced toxicity in the blood of Wistar rats

Abstract Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. The aim of our study was to investigate the prooxidative effects of nicotine and protective (additive or synergistic) effects of quercetin and vitamin C in the blood of experimental animals, to determine whether the combination of these antioxidants might be beneficial for clinical purposes. Wistar albino rats were receiving intraperitoneal nicotine injection (0.75 mg kg-1 per day) or saline (control group) or nicotine plus quercetin (40 mg kg-1 per day) and vitamin C (100 mg kg-1 per day) for three consecutive days. On day 4, we determined their blood lipid profile, liver enzymes, oxidative stress parameters, and antioxidative system parameters. Compared to untreated control, nicotine significantly increased total cholesterol, LDLcholesterol, triglycerides, liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) and oxidative stress parameters (superoxide anion, hydrogen peroxide, and lipid peroxide) and decreased HDL-cholesterol, glutathione, and superoxide dismutase/catalase activity. Quercetin + vitamin C reversed these values significantly compared to the nicotine alone group. Our results confirm that nicotine has significant prooxidative effects that may disrupt the redox balance and show that the quercetin + vitamin C combination supports antioxidant defence mechanisms with strong haematoprotective activity against nicotine-induced toxicity. In practical terms, this means that a diet rich in vitamin C and quercetin could prevent nicotine-induced toxicity and could also be useful in the supportive care of people exposed to nicotine.

Neuropeptide Y reduces migration capacity of human choriocarcinomacell line by altering oxidative/antioxidative status

Reduced migration capacity of trophoblast cells leads to poor placentation and correlates with severe pregnancy disorders such as intrauterine growth restriction and preeclampsia. Neuropeptide Y (NPY) is sympathetic cotransmitter involved in various physiological processes and its levels are significantly increased in preeclamptic pregnancy compared to healthy pregnancy. In this study the prooxidative role of NPY and its effects on migration capacity of human trophoblast cell line JEG-3 were investigated together with the effects of nitric oxide (NO) depletion, a molecule that was shown to play an important role in promoting cell migration. The cells were treated for 24 h (short-term stimulation) and 72 h (long-term stimulation) respectively with 1 nM NPY. Oxidative/antioxidative status and the migration index of cells were measured. The results showed increased concentrations of oxidative stress parameters (O2.-, H2O2) and molecules of the antioxidant defense system (reduced glutathione and oxidized glutathione), while the levels of intracellular nitrites (indicators of NO) and cell migration index were significantly decreased in trophoblast cells treated with NPY (both at 24 h and 72 h of exposure) compared to the control cells. These results suggest that NPY may significantly contribute to reduced migration capacity of trophoblast cells by generating oxidative stress and reducing the bioavailability of NO.