[Dosage-toxicity-efficacy relationship of Kansui Radix in malignant pleural effusion models based on Walker 256 analysis]

Abstract

To investigate the dosage-toxicity-efficacy relationship of Kansui Radix, explore its regularity of the toxicity and efficacy change, and provide scientific basis for its clinical rational application, the malignant pleural effusion models were used to observe the effect of Kansui Radix with larger dose range (0.045-1.620 g•kg•d⁻¹ for Kansui Radix) on biochemical indexes and hydrothorax volume in experimental animals. Factor analysis method was also used to comprehensively assess the dosage-toxicity-efficacy relationship of Kansui Radix. The results showed that the rats in model group had larger hydrothorax volume, and ALT, AST, LDH, HBDH, IFN-γ, IL-2 and TNF-α levels were significantly increased (P<0.05), while TP and ALB levels were decreased (P<0.05) as compared with the blank group. After drug administration, various treatment groups decreased hydrothorax volume, IFN-γ, IL-2, TNF-α and increased TP and ALB levels as compared with model group, indicating certain therapeutic effect; and increased ALT, AST, LDH and HBDH levels, indicating certain liver and cardiac toxicity. In the factor analysis, two common factors were extracted from nine indexes, explaining 89.1% of the information. The analysis results suggested that there was no obvious toxicity in case of independent use of Kansui Radix within the dosage range set in pharmacopeia, while it would produce liver toxicity and cardiac toxicity upon 3 times of the dosage set in pharmacopeia, and the toxicity was increased with the increase of dose. At the same time, Kansui Radix can decrease the hydrothorax volume in malignant pleural effusion models and improve relevant physical indexes in a dose-dependent manner. Comprehensive analysis results of its toxic effect characteristics indicated that the upper-limit dose of Kansui Radix in pharmacopeia shall be regarded as the relatively optimal therapeutic dose.

Keywords: Kansui Radix; dosage-toxicity-efficacy relationship; factor analysis; malignant pleural effusion.