Silibinin-loaded Nanostructured Lipid Carriers (NLCs) Ameliorated Lead-induced Acute Nephrotoxicity in Male Rats.

As a toxic heavy metal, lead (Pb) is well known for impairment of renal function due to oxidative injuries. In contrast, the antioxidant activity of silibinin has been approved. Given the role of silibinin antioxidant activity, the present study investigated the effectiveness of silibinin-loaded nanostructured lipid carriers (Sili-NLCs) against Pb-induced acute nephrotoxicity in rats. The emulsification-solvent evaporation method was applied to prepare Sili-NLCs. Sixty male Wistar rats were divided into ten separate groups. Pb (20 mg/kg/day, i.p.) was applied to induce nephrotoxicity and in the treatment groups animals received the same concentration of silibinin and Sili-NLCs (25, 50, and 100 mg/kg/day, p.o.) for five days. After sacrificing rats, kidney tissue samples were collected to assess the oxidative stress parameters, including lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity. Also, histopathological examination using Hematoxylin-Eosin (H&E) was studied. Not only did Pb injection significantly increase the renal levels of LPO and NO, but also decreased the levels of antioxidant enzyme activity. On the other hand, Sili-NLCs were more effective than silibinin in decreasing renal oxidative damage by increasing the antioxidant defense system. Moreover, the histopathological examination correlated well with biochemical findings. Our data suggested that Sili-NLCs are potentially superior to pure silibinin for attenuating Pb-induced acute nephrotoxicity.

Arsenic and Tau Phosphorylation: a Mechanistic Review.

Arsenic poisoning can affect the peripheral nervous system and cause peripheral neuropathy. Despite different studies on the mechanism of intoxication, the complete process is not explained yet, which can prevent further intoxication and produce effective treatment. In the following paper, we would like to consider the idea that arsenic might cause some diseases via inflammation induction, and tauopathy in neurons. Tau protein, one of the microtubule-associated proteins expressed in neurons, contributes to neuronal microtubules structure. Arsenic may be involved in cellular cascades involved in modulating tau function or hyperphosphorylation of tau protein, which ultimately leads to nerve destruction. For proof of this assumption, some investigations have been planned to measure the association between arsenic and quantities of phosphorylation of tau protein. Additionally, some researchers have investigated the association between microtubule trafficking in neurons and the levels of tau protein phosphorylation. It should be noticed that changing tau phosphorylation in arsenic toxicity may add a new feature to understanding the mechanism of poisonousness and aid in discovering novel therapeutic candidates such as tau phosphorylation inhibitors for drug development.

Aluminum neurotoxicity and autophagy: a mechanistic view.

It is strongly believed that aluminum is one of the insalubrious agents because of its neurotoxicity effects and influences on amyloid ß (Aß) production and tau protein hyperphosphorylation following oxidative stress, as one of the initial events in neurotoxicity. The autophagy process plays a considerable role in neurons in preserving intracellular homeostasis and recycling organelles and proteins, especially Aß and soluble tau. Thus, autophagy is suggested to ameliorate aluminum neurotoxicity effects, and dysfunction of this process can lead to an increase in detrimental proteins. However, the relationship between aluminum neurotoxicity and autophagy dysregulation in some dimensions remains unclear. In the present review, we want to give an overview of the autophagy roles in aluminum neurotoxicity and how dysregulation of autophagy can affect aluminum neurotoxicity.

Comparative efficacy of silibinin and nano-silibinin on lead poisoning in Male Wistar rats.

Lead (Pb) is an environmental neurotoxin that can lead to toxicity. It has shown that tissues can be exposed to oxidative stress in lead poisoning. Since silymarin is a natural agent with antioxidant effects, this study aimed to investigate the antioxidant and chelation effects of silibinin and nano-silibinin on the oxidative stress status in lead-poisoned rats. Sixty male Wistar rats randomly divided into ten groups (n = 6). Control and Pb groups treated with or without silibinin and nano-silibinin for six days. Following measuring of weight and blood lead levels, biochemical antioxidant parameters evaluated. Finally, a histopathological examination of the liver performed. In this experiment, silibinin and more efficiently nano-silibinin prevented weight loss and blood lead level elevation induced by lead. Also, they increased the attenuated levels of superoxide dismutase (SOD) activity, catalase (CAT), total thiol molecules (TTM), glutathione (GSH), and total antioxidant capacity (TAC). Lead-induced elevation of lipid peroxidation products (MDA) and nitric oxide (NO) normalized to the standard level in silibinin and especially nano-silibinin groups. These data suggested that silibinin and especially nano-silibinin can decrease blood lead levels and prevent weight loss and oxidative stress in the lead-poisoned rat's model.