Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats

Abstract

Paraquat (PQ) is a nonselective herbicide that induces oxidative reactions and multiple-organ failure on exposure. Crocin, a carotenoid obtained from saffron, has demonstrated many therapeutic effects against neural conditions because of its antioxidant properties. In this study, 30 male Wistar rats were divided into 6 groups to evaluate the protective effects of crocin and crocin-loaded niosomes (NC) against PQ in the brain. The levels of total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), superoxide dismutase (SOD), and catalase (CAT) activity were measured as the markers of redox status. Histopathological changes in the CA1 region of the hippocampus were evaluated by cresyl violet staining. Results indicated that both crocin and NC were able to attenuate the adverse effects of PQ at the histopathological level, which was following the changes in LPO (P < 0.0001), TAC (P < 0.01), and TTG (P < 0.05) level. The activity of CAT (P < 0.01) and SOD (P < 0.01) could be restored either by crocin or NC. Also, results indicated that nanoformulation of crocin in niosomes appears to be more promising. In conclusion, both crocin and NC showed favourable effects of PQ in the brain of rats, and were determined to be excellent agents to prevent acute toxicities of PQ. Furthermore, these two compounds can be known to provide neuroprotection.

Keywords: brain; crocin-loaded niosomes; oxidative stress; paraquat; rats.

Figure 1

Effects of crocin and NC on LPO in rat brain tissue. PQ: Paraquat (5 mg/kg/day for 7 days by IP); Crocin (20 mg/kg/day for 7 day by IP); NC: crocin loaded niosomes (20 mg/kg/day for 7 day by IP). **** indicates significant difference with control (P < 0.0001), and ^#### indicates significant difference with group P (P < 0.0001).

Figure 2

Effects of crocin and NC on TAC of brain tissue. PQ: Paraquat (5 mg/kg/day for 7 days by IP); Crocin (20 mg/kg/day for 7 days by IP); NC: crocin loaded niosomes (20 mg/kg/day for 7 day by IP). **** indicates significant difference with control (P < 0.0001), and ^## (P < 0.01), ^### (P < 0.001) indicates significant difference with group P (P < 0.001). aa indicates significant difference with Crocin and crocin loaded niosomes treatment group (P < 0.01).

Figure 3

Effects of crocin and NC on TTG of brain tissue. PQ: Paraquat (5 mg/kg/day for 7 days by IP); Crocin (20 mg/kg/day for 7 days by IP); NC: crocin loaded niosomes (20 mg/kg/day for 7 days by IP). ** indicates significant difference with control (P < 0.01), and ^# (P < 0.05), ^### (P < 0.001) indicates significant difference with group PQ (P < 0.001).

Figure 4

Effects of crocin and NC on CAT activity of the brain. PQ: Paraquat (5 mg/kg/day for 7 days by IP); Crocin (20 mg/kg/day for 7 days by IP); NC: crocin loaded niosomes (20 mg/kg/day for 7 days by IP). **** indicates significant difference with control (P < 0.0001), and ^## (P < 0.01), ^#### (P < 0.0001) indicates significant difference with group PQ (P < 0.001). a indicates significant difference with crocin and crocin loaded niosomes treatment group (P < 0.05).

Figure 5

Effects of crocin and NC on SOD activity of the brain. PQ: Paraquat (5 mg/kg/day for 7 days by IP); Crocin (20 mg/kg/day for 7 days by IP); NC: crocin loaded niosomes (20 mg/kg/day for 7 days by IP). *** (P < 0.001), **** (P < 0.0001) indicates significant difference with control), and ^## (P < 0.01) indicates significant difference with group PQ.

Figure 6

Effects of crocin and NC on histopathological changes in the CA1 region of the hippocampus. Assessed by cresyl violet staining, 40× magnification. Rats were exposed to paraquat + crocin or NC for 7 days. (a) Control, (b) Crocin, (c) NC (d) Paraquat, (e) Paraquat + Crocin, and (f) Paraquat + NC. Arrows indicate cell density in the hippocampal CA1 region.

Figure 7

Effects of crocin and NC on histopathological changes in the CA1 region of the hippocampus. Results are expressed as Mean value ± SEM. a indicates a significant difference with group Control (P < 0.001); and b (P < 0.01) as well c (P < 0.001) indicate a significant difference with group Paraquat.