3.4. In vivo hepatotoxicity evaluat

3.4. In vivo hepatotoxicity evaluations After satisfactory in vivo pharmacokinetic studies, the liver protective effect of SYA in the cocrystal was further evaluated, and the serum levels of TA, ASA and ALA for 4 groups (untreated controls, pure INH, the cocrystal and the physical mixture of INH and SYA) are given in Fig. 9. As illustrated in Fig. 9a, compared with untreated controls, the TA value of the pure INH group (without SYA) showed a significant decrease, which may be due to the fact that in terms of taking INH could strike the balance between antioxidants and prooxidants thus damage the liver seriously [31]. It is noteworthy that owing to the antioxidant capacity of SYA, the co-administration of SYA with INH by the form of physical mixture produced some increase in TA value, however, it was still lower than that of the untreated control, owing to the confirmed low bioavailability of SYA. In contrast, the treatment with the cocrystal could signally improve the value of TA and make the value reach that reported in the untreated control. Obviously, the cocrystal formation can enhance the antioxidant ability of SYA and protect the liver from injuring. The alterations in liver enzymes levels could further demonstrate the above observations. As shown in Fig. 9b, the treatment with pure INH (without SYA) produced a significant increase in ASA and ALA levels due to the hepatotoxicity of INH. While in the cocrystal group, the elevations levels of ASA and ALA activities were effectively attenuated, and reached to those of untreated controls. These results certified that cocrystallization SYA with INH almost eliminated isoniazid induced hepatotoxicity, which exhibited a promising advantage of clinical effects