Protein a Induced Abrogation of Cyclophosphamide Toxicity is Associated with Concomitant Potentiation of Immune Function of Host

Abstract

This report confirms our previous observation that protein A (PA) of Staphylococcus aureus Cowan I reduces the cyclophosphamide (Cy) induced toxicity. PA treated animals recover quickly from the toxic effects of Cy. We have exhaustively studied the role of specific and nonspecific immunity in the protection of the animals. It was observed that PA helped the animals in the accelerated regeneration of leukocytes of blood (p less than 0.001) and different lymphoid organs like thymus (p less than 0.001), spleen (p less than 0.01) and bone marrow (p less than 0.01). Increased number and function of macrophages was also observed in PA (p less than 0.001) and PA+Cy (p less than 0.001) groups. PA, on one hand enhanced the cell mediated immunity while suppressed the humoral immunity as was assessed by increase in delayed type hypersensitivity response (p less than 0.001) and decreased in plaque forming cells (p less than 0.001), EAC-rosettes (p less than 0.001), hemagglutination (p less than 0.001) and hemolysin titre (p less than 0.05). On the basis of above observations we propose that the immunomodulatory activity of PA helped the animals to remain alive in two ways- (1) by early generation of the cells depleted by the Cy thus helping animals to repair the damaged immune system and fast clearance of the toxic metabolites of Cy (2) by temporarily suppressing the cells responsible for humoral immunity which are more susceptible to Cy metabolites.

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice

“…Toxic effects of CP towards humoral immunity, especially B-cell functions are well documented and we have also reported the same in our previous investigations. 13,17,31,32 E. officinalis at a dose of 100 mg/kg caused an increase in the splenic cell counts. Conversely, it decreased the relative organ weight of spleen.…”

“…Studies have been conducted using CP along with some protective agent(s). For example, Ray et al, 11 Dohadwala and Ray 12 and Zaidi et al 13 have shown that the immunomodulating agent, protein A of Staphylococcus aureus, protects animals from CPinduced toxicity. We have also shown that CPinduced in vitro and in vivo mutagenicity could be inhibited by the herbs Cassia occidentalis and Emblica officinalis.…”

Studies of the Safety, Pharmacokinetics and Immunogenicity of Repeated Doses of Intravenous Staphylococcal Protein A in Cynomolgus Monkeys

“…SPA treatment was associated with increases in glutathione‐S‐transferase. One prior safety study of intravenous SPA in the monkey was found in the published literature . However, this non‐GLP pilot study did not characterize the origin or purity of the SPA utilized for dosing and contained no toxicokinetic information on the plasma exposures attained.…”

Modulatory Effect of a Unani Formulation (Jawarish amla sada) on Cyclophosphamide-induced Toxicity in Tumour Bearing Mice

“…CP also induces mutagenicity in mice (Sharma et al, 2001). The suppressive effects of CP on lymphoid organs, WBC counts and other immune functions are well documented (Zaidi et al, 1990;Bin-Hafeez et al, 2001;Jena et al, 2003;Ramadan et al, 2011;Shreder et al, 2012).…”