Synthesis of Fluorescent Pyrrolo[1,2-a]pyrimidines from Fischer Carbene Complexes as Building Blocks.

A novel synthetic methodology is reported for the synthesis of fluorescent pyrrolo[1,2-a]pyrimidines. Fischer carbene complexes served as the synthetic platform for (3+3) cyclization to form the heterocyclic moiety. The reaction process furnished two products, their ratio being modulated by the metal, base, and solvent. The selectivity exhibited was studied by analyzing the potential energy surface with density functional theory tools. The photophysical properties of absorption and emission were also evaluated. The dyes absorbed at wavelengths of 240-440 nm, depending on the substituents. The maximum emission wavelength was in the range of 470-513 nm, with quantum yields of 0.36-1.0 and a high Stokes shift range of 75-226 nm.

Melatonin therapy reverses lead exposure-induced testicular damage in rats despite the lack of effect on serum testosterone levels.

Lead (Pb) exposure induces testicular damage and infertility. The aim of this study was to analyze and compare the therapeutic effects of antioxidants or vitamin D and calcium, which have previously been shown to reduce the toxic effects of Pb co-exposure, in rats. Rats were exposed to Pb for 28 days and subsequently treated with antioxidant (melatonin, silymarin), vitamin D and calcium (VitDCa) or a combination (melatonin or silymarin with VitDCa) for 28 days. Control groups included untreated rats (no Pb exposure or therapy), rats exposed only to melatonin or silymarin and rats exposed to Pb without post exposure therapy. Pb exposure induced testicular damage, increased blood lead level (BLL) and reduced serum testosterone level (STL). Rats exposed to Pb and left untreated for 28 days showed persistent pathological testicular alterations. The two treatments that were most effective in reversing pathological testis damage and restoring spermatogenesis were melatonin and silymarin. However, silymarin and melatonin treatment resulted in significantly different serum testosterone levels in rats. Whereas melatonin therapy reduced serum testosterone to levels lower than those in control rats, silymarin increased serum testosterone to levels higher than those in controls. Our pathological analysis of testes revealed that melatonin promoted spermatogenesis and regression of Pb exposure-induced degenerative changes, despite the associated reduction in serum testosterone levels. This result suggests that circulating testosterone may not have an important role in spermatogenesis. Collectively, our results suggest that melatonin and silymarin are effective therapies against the toxic effects Pb exposure in the male reproductive system.

Melatonin attenuates the effects of sub-acute administration of lead on kidneys in rats without altering the lead-induced reduction in nitric oxide.

Exposure to lead induces oxidative stress and renal damage. Although most forms of oxidative stress are characterized by simultaneous elevation of nitrogen and oxidative species, lead-induced oxidative stress is unusual in that it is associated with a reduction in nitric oxide (NO) levels in the kidney. The role of NO in kidney injury is controversial; some studies suggest that it is associated with renal injury, whereas others show that it exerts protective effects. Concentration-dependent effects have also been proposed, linking low levels with vasodilatation and high levels with toxicity. The aim of this study was to evaluate the effects of melatonin co-exposure on the lead-induced reduction in renal NO levels. We found that sub-acute intraperitoneal administration of 10 mg/kg/day of lead for 15 days induced toxic levels of lead in the blood and caused renal toxicity (pathological and functional). Under our experimental conditions, lead induced an increase in lipid peroxidation and a decrease in NO. Melatonin co-treatment decreased lead-induced oxidative stress (peroxidation level) and toxic effects on kidneys without altering the lead-induced reduction in renal NO. These results suggest that, in our experimental model, the reduction in renal NO levels by lead exposure is not the only responsible factor for lead-induced kidney damage.

Effect of glycine on lead mobilization, lead-induced oxidative stress, and hepatic toxicity in rats.

The effectiveness of glycine in treating experimental lead intoxication was examined in rats. Male Wistar rats were exposed to 3 g/L lead acetate in drinking water for 5 weeks and treated thereafter with glycine (100 and 500 mg/kg, orally) once daily for 5 days or glycine (1000 mg/kg, orally) once daily for 28 days. The effect of these treatments on parameters indicative of oxidative stress (glutathione and malondialdehyde levels), the activity of blood δ-aminolevulinic acid dehydratase, and lead concentration in blood, liver, kidney, brain, and bone were investigated. Liver samples were observed for histopathological changes. Glycine was found to be effective in (1) increasing glutathione levels; (2) reducing malondialdehyde levels; (3) decreasing lead levels in bone with the highest dose. However, glycine had no effect on lead mobilization when 100 and 500 mg/kg glycine were administered. In microscopic examination, glycine showed a protective effect against lead intoxication.

Oxidative stress effects of thinner inhalation.

Thinners are chemical mixtures used as industrial solvents. Humans can come into contact with thinner by occupational exposure or by intentional inhalation abuse. Thinner sniffing causes damage to the brain, kidney, liver, lung, and reproductive system. We discuss some proposed mechanism by which thinner induces damage. Recently, the induction of oxidative stress has been suggested as a possible mechanism of damage. This paper reviews the current evidence for oxidative stress effects induced by thinner inhalation. Early ideas about the effects of thinner on lipids are discussed in one section. We discuss several studies that have shown the oxidative effects of thinner inhalation on: lipid peroxidation, levels of antioxidant enzymes, glutathione depletion, and oxidation of proteins and DNA. We have also included studies about oxidative stress effects induced by toluene, the principal component (60-70%) of thinner. Finally, work describing the effects of oxidative stress induced by thinner inhalation on different organs is discussed.