Original Article

Acute toxicity of PSD-007 (a new hematoporphyrin photosensitizer) in mice and dogs

Authors: Nian-ci SHEN, Bo-jin YUAN, Hui-lan TANG, Bao-chun LI, Jun-ping LIU, Yan-ping LI, Pu ZHANG

Abstract

PSD-007 is a new hematoporphyrin photosen sitizer prepared in our laboratory. The 95% fiducial limits of its iv LD50 on mice were 176-236 mg/kg. Its iv minimal lethal dose (MLD) and approximate lethal dose (ALD) on dogs were 171 and 114 mg/kg, respectively. Since all these toxic doses were over 20 times as much as usual clinical dosage (2.5-5.0 mg/kg iv), its toxicity was considered to be low.
The manifestations of its acute iv toxicity were characterized by a complex syndrome like acute abdominal pain with various neurologic features ranging from nausea, vomiting, restlessness, howl, hoarseness, analgesia, paresis and paralysis. These manifestations were similar to those seen in porphyrias, a metabolic defect seldom seen clinically. The hematopoietic features including RBC, WBC, and hematocrit were reduced markedly. The elevated activities of sGPT, serum phosphohexoisomerase, the increased amounts of RBC, WBC, protein and occasional appearance of casts in urine demonstrated that hepatic and renal functions were impaired to some extent. All these damage were reversible within 2 week. These results may be useful for the control of its side effects during clinical use.
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