## 4 Discussion
Diabetic mellitus is mainly associated with multiple metabolic disorders, among which lipid metabolism is comparatively affected resulting in higher concentrations of TG and TC and low levels of HDL-cholesterol [38]. In the current study, TC (139.37 \(\pm\) 8.7 mg/dL), TG (238.7 \(\pm\) 7.2 mg/dL), LDL-cholesterol (167.9 \(\pm\) 7.2 mg/dL) levels were significantly increased and HDL-cholesterol decreased (38.6 \(\pm\) 7.2 mg/dL) in STZ-treated diabetic rats. The treatment with TQ caused a significant reduction of TC (117.23 \(\pm\) 4.7 mg/dL), TG (201.23 \(\pm\) 9.4 mg/dL), LDL-cholesterol levels (132.3 \(\pm\) 9.4 mg/dL). Moreover, the decreased serum HDL-cholesterol in diabetic animals was also upturned toward the normal level (61.9 \(\pm\) 9.4 mg/dL) after the treatment with TQ. Previous findings were in accordance with the current results and it was demonstrated that a significant decline in serum triglyceride levels in diabetic animals treated by TQ [39] and _Nigella sativa_ significantly decreased LDL-lipoproteins [40]. TQ administration decreases protein carbonyls and serum level of TC, LDL-C, TG, and MDA through decreasing the oxidative stress. TQ also improves the activity of arylesterase accompanied by decrease in the activity of HMG-CoA reductase [41]. STZ induces experimental diabetes in rats [42], thereby producing elevated levels of liver function enzymes ALT, AST, and ALP and this is a good indicator of liver damage. ALT and AST are directly linked with the reaction of amino acids to keto acids and are designated to increase in diabetic conditions [43]. The present study demonstrated the increased activities of serum liver function enzymes, ALT (187.5 \(\pm\) 9.0 U/L), AST (194.6 \(\pm\) 3.0 U/L), ALP (153.2 \(\pm\) 3.0 U/L) level, designated that hepatotoxicity might be due to induction of hyperglycemia via STZ induction. The current finding reported that the treatment of STZ -treated diabetic rats with TQ leads to a substantial reduction in levels of liver function enzymes, ALT (120.5 \(\pm\) 8.0 U/L), AST (139.3 \(\pm\) 9.0 U/L), ALP (112.6 \(\pm\) 9.0 U/L) towards normal levels that evidences that TQ protect liver cells. Previous finding demonstrated that beneficial effects of thymoquinone on hepatic key enzymes in diabetic rats [44]  
Lipid peroxidation provides a sign of cellular damage mediated through ROS [45]. The high levels of ROS causes membrane lipid peroxidation in addition to the production of malondialdehydedehyde (MDA). Liver MDA levels were significantly higher in STZ-induced rats and it was also observed that TQ supplementation significantly decreased the hepatic lipid peroxidation. Inflammation play an important role in diabetes development and is thus associated with enhanced insulin resistance and reduced response in insulin target tissues [46]. Moreover, NF-k\(\beta\) and TNF-\(\alpha\) are vital indicators of insulin resistance and pancreatic \(\beta\)-cells dysfunction, causative to the development of diabetes mellitus [47]. The circulating levels of the most proinflammatory cytokines are usually elevated in diabetes mellitus, mainly as a result of hyperglycemia, which stimulate the blood levels of cytokines to increase through an oxidative mechanism [48; 49]. Previous reports based on in vivo and in vitro based studies reported that TQ plays a role in the reduction of pro-inflammatory cytokines such as IL-6, Cox-2, and TNF-\(\alpha\)[50; 51]. In this study, we reported that TQ inhibited the overproduction of inflammatory cytokines in STZ-treated diabetic animals because of its the anti-inflammatory responses. The actual mechanism of STZ-treated diabetes in rats primarily involves ROS production, DNA alkylation, and overproduction of nitric oxide (NO) in pancreatic \(\beta\)-cells [42]. The loss of \(\beta\)-cell mass as well as its function is the main reason of the development of DM and causes B cell dysfunction [52; 53].