» Articles » PMID: 34410951

Inhibition of Toll Like Signaling Pathway Is Associated With Genomic Instability in Rat Liver Exposed to Crack Cocaine

Abstract

Background/aim: The aim of the present study was to investigate the biological effects of subacute crack cocaine exposure in rat liver.

Material And Methods: A total of 32 rats were distributed into four groups (n=8): Experimental group 1 (G1) and Experimental group 2 (G2): rats received 18 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day, group G2 remained 72 h without exposure after the experimental period (5 days)(abstinence); Experimental group 3 (G3): rats received 36 mg/kg of body weight (b.w) of crack cocaine for 5 days, once a day; Control Group (CTRL): rats received only the vehicle (DMSO) administered by the intraperitoneal (i.p) route for 5 days, once a day.

Results: All groups exposed to crack cocaine had an increase in the number of micronucleated hepatocytes and binucleated cells only in the highest tested dose (36 mg/kg). Karyolysis had an increase in the 18 mg/kg dose, in the abstinence group (G2), and 36 mg/kg group (G3); whereas pyknotic nuclei had an increase in the G2 group. The group exposed to 18 mg/kg of crack cocaine also showed high 8 OHdG expression. The p-NF-κB p65 protein decreased in the groups exposed to crack cocaine at doses of 18 and 36 mg/kg, as well as in the abstinence group. MyD88 was also found decreased in the group exposed to crack cocaine at 18 mg/kg.

Conclusion: Crack cocaine inhibited toll like signaling pathway whilst being associated with genomic instability in rat liver cells.

References
1.
de Freitas T, Palazzo R, de Andrade F, Reichert C, Pechansky F, Kessler F . Genomic instability in human lymphocytes from male users of crack cocaine. Int J Environ Res Public Health. 2014; 11(10):10003-15. PMC: 4210963. DOI: 10.3390/ijerph111010003. View

2.
Periyasamy P, Liao K, Kook Y, Niu F, Callen S, Guo M . Cocaine-Mediated Downregulation of miR-124 Activates Microglia by Targeting KLF4 and TLR4 Signaling. Mol Neurobiol. 2017; 55(4):3196-3210. PMC: 5673594. DOI: 10.1007/s12035-017-0584-5. View

3.
Chivero E, Liao K, Niu F, Tripathi A, Tian C, Buch S . Engineered Extracellular Vesicles Loaded With miR-124 Attenuate Cocaine-Mediated Activation of Microglia. Front Cell Dev Biol. 2020; 8:573. PMC: 7409518. DOI: 10.3389/fcell.2020.00573. View

4.
Riezzo I, Fiore C, De Carlo D, Pascale N, Neri M, Turillazzi E . Side effects of cocaine abuse: multiorgan toxicity and pathological consequences. Curr Med Chem. 2012; 19(33):5624-46. DOI: 10.2174/092986712803988893. View

5.
Claudio S, Pidone Ribeiro F, de Lima E, Santamarina A, Pisani L, Pereira C . The protective effect of grape skin or purple carrot extracts against cadmium intoxication in kidney of rats. Pathophysiology. 2020; 26(3-4):263-269. DOI: 10.1016/j.pathophys.2019.07.001. View