The effects of L-citrulline adjunctive treatment of Toxoplasma gondii RH strain infection in a mouse model

Toxoplasma gondii is a zoonotic intracellular protozoan parasite and its therapeutic limitations are one of its
major problems. L-citrulline is an organic compound that has beneficial effects on many diseases. The purpose of
this study was to assess the impact of L-citrulline, alone or in combination with sulfamethoxazole-trimethoprim
(SMZ-TMP) on acute toxoplasmosis caused by Toxoplasma gondii RH virulent strain. In our study, 60 Swiss albino
mice were divided into two main groups; the control group and the infected treated group, which was subdivided
into group IIa: infected treated with L-citrulline, group IIb: infected treated with SMZ-TMP, and group IIc:
infected treated with L-citrulline combined with SMZ-TMP. The effects of treatment were assessed by parasitological study, electron microscopic study of tachyzoites, and histopathological study of the liver. Moreover,
ELISA measurement of the serum level of Interferon-gamma, Interleukin 10, Nitric oxide, and apoptotic markers
was used. It was noticed that L-citrulline combined with SMZ-TMP significantly increased the survival time of
infected mice with a significant decrease in the number of tachyzoites compared to the other groups. Moreover, it
increased the levels of measured cytokines and serum anti-apoptotic proteins Bcl-2 and improved the extent of
liver cell damage associated with a decrease in inflammatory infiltration. In conclusion, L-citrulline supplementation was found to be effective against acute toxoplasmosis, especially when combined with SMZ-TMP as it
has multifactorial mechanisms; nitric oxide production, anti-inflammatory, anti-apoptotic, and immune
stimulator.