Assessing the toxicity of pesticides exposure on hepatic miRNA-target gene alterations in rat liver tissues via molecular and integrated network bioinformatics analysis.

The prevalent use of pesticides, including pirimiphos-methyl (PPM) and bifenthrin (BF), poses a serious health risk, particularly to workers who encounter these chemicals daily. Despite the recognized hepatotoxic effects, the specific molecular mechanisms, especially those involving miRNAs in liver damage caused by PPM and BF, are not fully elucidated. Prior studies have not exhaustively analyzed the hepatic miRNA-target gene dynamics following exposure to these pesticides; thus, this research aims to fill that gap through an extensive miRNA analysis to discern their regulation in PPM or BF-induced hepatic toxicity. In this study, male Sprague-Dawley rats were exposed to BF or PPM for 28 days through oral gavage, simulating the chronic exposure faced by humans. We conducted a thorough assessment of the hepatotoxicity induced by PPM and BF, employing multiple evaluation levels, including histological analysis, liver enzyme measurements, and real-time PCR to detect changes in hepatic miRNA-target gene expressions. Additionally, we utilized DIANA-miRPath prediction tools to delineate the functional implications of these hepatic miRNA target genes. Our findings reveal a significant modulation in the expression of rno-miR-155-5p and rno-miR-122-5p, along with their target genes, following PPM and BF treatment. In contrast, rno-miR-21-5p levels remained unaltered. These observations suggest potential utility of these specific hepatic miRNAs as biomarkers for liver injury resulting from pesticide exposure. Subsequent GO enrichment analysis linked target genes to functions like molecular activity, protein binding, and cellular processes. Additionally, KEGG pathway analysis showed these genes, influenced by varied miRNA expressions, play significant roles in metabolic and signaling pathways In conclusion, this study enhances our comprehension of the biological roles of miRNAs in hepatic toxicity induced by PPM and BF. The insights gained here not only shed light on molecular mechanisms but also open avenues for considering these miRNAs as potential diagnostic biomarkers in conditions of pesticide-induced hepatotoxicity, thereby guiding future therapeutic strategies.

The role of stinging nettle (Urtica dioica L.) in the management of rotenone-induced Parkinson's disease in rats.

Parkinson's disease (PD) is one of the most common neurodegenerative conditions. Alpha-synuclein deposition, Lewy bodies (LBs) formation, disruption of the autophagic machinery, apoptosis of substantia nigra dopaminergic neurons, oxidative stress, and neuroinflammation are all pathologic hallmarks of PD. The leaves of the stinging Nettle (Urtica dioica L.) have a long history as an herbal cure with antioxidant, anti-inflammatory, anti-cancer, immunomodulatory, and neuroprotective properties. The current study aims for the first time to investigate the role of Nettle supplementation on Rotenone-induced PD. Rats were divided into five groups; a Saline control, Nettle control (100 mg/kg/day), Rotenone control (2 mg/kg/day), Rotenone + Nettle (50 mg /kg/day), and Rotenone + Nettle (100 mg/kg). After four weeks, the rats were examined for behavioral tests. The midbrains were investigated for histopathological alteration and immunohistochemical reaction for Tyrosine hydroxylase in the dopaminergic neurons, α-synuclein for Lewy bodies, caspase 3 for apoptotic neurons, LC3 and P62 for autophagic activity. Midbrain homogenates were examined for oxidative stress markers. mRNA expression of TNFα and Il6; inflammatory markers, Bcl-2, BAX and Caspase 3; apoptosis markers, were detected in midbrains. The results showed that Nettle caused recovery of midbrain dopaminergic neurons, by inhibiting apoptosis, inflammation, and oxidative stress and by restoring the autophagic machinery with clearance of α-synuclein deposits. We can conclude that Nettle is a potentially effective adjuvant in the treatment of Parkinson's disease.