Histological vis-a-vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt-ATP on experimental animal models.
BACKGROUND
Cisplatin, a platinum based anticancer drug has played a vital role in the treatment of cancers by chemical agents, but in view of the serious toxicity including nephrotoxicity of cisplatin, various other platinum based drugs have been synthesized and screened to overcome its toxicity. A Pt-ATP compound was prepared in our laboratory hoping to have reduced or no toxicity along with the potentiality of reducing neoplasm growth.


METHODS
A Pt-ATP compound was prepared. It was first screened for its antineoplastic efficacy. Confirming that, subsequent experiments were carried on to test its toxicity on animals, viz. Albino Swiss mice. The animals were randomly divided into four sets--Set I: Erhlich Ascites Carcinoma (EAC) challenged mice; Set II: Normal mice; Set III: Drug treated mice, Set IVA Cisplatin (CDDP) treated mice, Set IV B EAC challenged Cisplatin treated mice. Set I was used to test antineoplasticity of the drug, Set II and Set III for studying drug toxicity and Set IV was treated with CDDP. Set II was used as a control. Animals were sacrificed after 5 days, 10 days 15 days and 20 days of drug administration on the 6th, 11th, 16th and 21st days respectively for Set I, II and III. Set IVA was sacrificed only on the 16th day and Set IV B on 6th and 11th days. For Set I only tumor cell count and packed cell volume (PCV) of tumor cells were recorded. For Set II and III, aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. For cytotoxicity assessment liver, spleen and kidney tissues were collected and subjected to scanning electron microscopy (SEM) after extensive treatment. Set IV A was only studied for the biochemical parameters viz. aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. Set IV B was studied for tumor cell count after treatment with CDDP for 10 days.


RESULTS
Our comparative studies with normal and drug treated animals reveal that the drug does not affect the body weight of the drug treated animals significantly. The biochemical parameters like ALT and AST levels are also within normal limits which rules out hepatotoxicity. The detailed histological studies by SEM reveal that the hepatic, kidney and spleen tissues are not adversely affected by the drug. Comparison of biochemical parameters with the CDDP treated animals show that Pt-ATP is not at all toxic like the CDDP. The Kaplan-Meier analysis of the survival data of Set I has shown promising results with a significance of p < 0.0001.


CONCLUSIONS
Set I results are promising and indicating antineoplastic efficacy of the synthesized drug with increased life span of the animals. Biochemical analysis, hematological and SEM studies revealed that the drug was neither nephrotoxic nor hepato-spleeno-toxic under the experimental set up.
Pal
Shipra
S
Department of Chemistry, Jadavpur University, Kolkata - 700032, India. nikupal@yahoo.co.in
Sadhu
Arpita Sengupta
AS
Patra
Swarup
S
Mukherjea
Kalyan K
KK
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C069451:platinum dichloride-adenosine triphosphate complex; D000255:Adenosine Triphosphate