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.