Potential role of a newly AChE reactivator in the depressive-like behavior induced by malathion.

AChE inhibition caused by exposure to organophosphate (OP) compounds is strongly related to behavioural disorders such as depression. Malathion is an OP that already has a relationship between its exposure and behavioural changes, although few data still have its effects in a longer exposure protocol. In addition, intoxication therapy is based on the use of atropine-oxime which still has its controversial efficacy depending on the type of compound. For this, (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that has properties of isatin and oxime in its structure, have shown reactivating properties in the activity of AChE that have been added to antidepressant-like effects in rats exposed to malathion in acute protocol. In this sense, effects of Cℓ-HIN on the depressive-like behaviour and AChE activity were evaluated in a protocol of subchronic exposure to malathion in rats. Male wistar rats were co-treated with Cℓ-HIN [5 mg/kg, p.o.] and/or malathion [1 or 10 mg/kg, i.p] for 20 days. The exposure to both doses of malathion increased immobility time of rats on the forced swimming test (FST). Besides, malathion inhibited the AChE activity in the prefrontal cortex of rats, but any significant difference was observed in the hippocampus. Cℓ-HIN protected against increased immobility time in the FST of those rats exposed to a dose of 1 mg/kg of malathion. Similarly, Cℓ-HIN was able to reactivate AChE activity only in that group exposed to the lowest dose of malathion. Collectively, the results of this study suggest that Cℓ-HIN is an oxime capable of reactivating AChE inhibited and presents na antidepressant-like effect in cases of prolonged exposure to malathion.

Assessment of unloaded polymeric nanocapsules with different coatings in female rats: Influence on toxicological and behavioral parameters.

The unloaded polymeric nanocapsules (NCs) present incredible characteristics as drug carriers. However, the toxicity caused by NCs with different coatings is still a challenge for contemporary toxicology. Allied to this, preclinical studies are performed in males, disregarding possible gender-dependent toxicity. Thus, the aim of present study was to evaluate the influence of different NCs coatings on toxicological and behavioral parameters in female rats. The physicochemical characterization of NCs with different surface coatings: NC1 (Polysorbate 80), NC2 (PEG), NC3 (Eudragit®RS 100) and NC4 (Chitosan) were performed. Female rats were treated with saline, NC1, NC2, NC3 or NC4 daily for 14 days, p.o. After 24 h of last treatment, animals were submitted to behavioral tests. Only after behavioral tests, female rats were euthanized, organs were removed and weighted. After, histopathological, biochemical and oxidative stress analysis were performed. All NCs-coatings did not cause alterations in behavioral tests. For markers of hepatic, renal damage and lipid profile, the different coatings showed a low toxicity. NCs did not alter weight of organs and histopathological analysis. Also, all NCs-coatings did not modify redox balance in organs studied, only NC2 induced a increase of FRAP levels in intestine. This study demonstrated that the different NCs-coatings did not cause behavioral changes and showed a low toxicity in female rats.

Cationic and anionic unloaded polymeric nanocapsules: Toxicological evaluation in rats shows low toxicity.

The experimental design aiming at evaluating the performance of drugs nanoencapsulated involves inclusion of a formulation without drug (unloaded). This formulation has sometimes presented per se effect. In this sense, we sought to evaluate the toxicity of unloaded polymeric nanocapsules (NCs) with different surfaces (cationic and anionic) in male Wistar rats in male Wistar rats. The physicochemical characterization of NCs with different surfaces: polysorbate 80 (P80), polyethylene glycol (PEG), eudragit ®RS 100 (EUD) and chitosan (CS) was performed. Rats were treated with unloaded NCs (P80, PEG, EUD and CS surfaces) daily for 14 days per oral route. 24 h of last treatment, animals were euthanized and organs were removed and weighted. After, biochemical determinations were performed. In general, NCs-surfaces did not cause alterations in body weight, weight of organs and histopathological analysis. PEG-surface NCs did not generate hepatotoxicity. In investigation of lipid profile, the surface with P80 changed TC and HDL-C levels. Besides that, all NCs did not alter oxidative stress markers in organs studied (TBARS and Reactive Species) and CS-surface presented antioxidant activity in kidney. This study demonstrated that NCs-surfaces depending on their physicochemical characteristics had low or no toxicity.