3.4 Lysine largely suppresses PQ-induced pulmonary fibrosis and mortality
To clarify whether lysine is sufficient to normalize PQ-raised pulmonary fibrosis, we then verified the therapeutic effects of lysine in vivo . PQ poisoning raised a continuous weight loss in mice, whereas administration of lysine impressively recovered and normalized the weight loss after long time treatment (Fig. 3A). Importantly, all the PQ-poisoned mice exhibited consistent trend of weight loss, whereas administration of lysine in PQ-poisoned mice exhibited individual difference, which some of the mice were instantly resistant to PQ poisoning with lysine treatment, others exhibited a reduction of weight loss and were ultimately recovered (Fig. 3B), indicating that a continuous treatment of lysine would be beneficial for neutralizing the toxicity of PQ. Nevertheless, treatment with lysine in PQ-poisoned mice largely increased the survival rate, which PQ-poisoned mice all died at day 7 whereas 62.5% mice were survived with lysine treatment (Fig. 3C). Consistently, the hydroxyproline levels increased by PQ were significantly alleviated by co-administration with lysine (Fig. 3D). The pulmonary fibrosis and alveolitis induced by PQ were amazingly healed, accompanied with an increased food intake and water intake in lysine treated group (Fig. 3E, Supplemental Fig. 1A-C). Consistently, PQ-induced damages in liver and kidney were largely recovered by lysine treatment, indicated by ALT, AST, or Creatine levels in blood (Fig. 3F-3H). Observations of lysine in treating PQ-poisoned mice model raised the potency of lysine in anti-PQ poisoning and PQ-raised pulmonary fibrosis in humans. Indeed, lysine in plasma was largely reduced in PQ-poisoned patients (Fig. 3I), making administration of lysine be reasonable for PQ-poisoned patients. Taken together, these results strongly suggested that lysine is the antidote for PQ poisoning and would be a potential strategy for PQ-raised pulmonary fibrosis.