Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats

Abstract

Purpose: Cisplatin, one of the most effective anticancer drugs, is known to cause undesirable adverse effects, including immunotoxicity. Echinacea purpurea is an important medicinal plant with immunostimulatory and anti-inflammatory activities. We have investigated the protective effect of an herbal formulation (Immulant) containing E. purpurea extract against cisplatin-induced immunotoxicity in rats.

Methods: Forty mature albino rats were randomized into four groups (10 rats/group). Control (group 1) animals were subjected to intraperitoneal (i.p.) injection of saline solution (0.2 ml) once every 3 days. Group 2 animals received cisplatin (3.5 mg/kg, i.p.) once every 3 days for successive 2 weeks. Group 3 rats received oral Immulant (150 mg/kg) once daily for 2 weeks. Group 4 animals received oral Immulant treatment as in group 3 in addition to cisplatin as in group 2. Serum level of total protein and albumin, total and differential leukocytic count, phagocytic activity of monocytes, humoral activity and splenic histopathology and immunohistochemistry were used as diagnostic markers of immunotoxicity.

Results: Cisplatin induced marked inhibition of cellular immunity as exhibited by significant decrease of leukocytic count, lymphocyte percentage and phagocytic activity with marked increase in neutrophil percentage. Humoral immunity represented by marked inhibition in total protein and γ-globulin concentration and significant inhibition in antibody titer against Mycoplasma gallisepticum were recorded. Histopathological and immunohistochemical observation of the spleen of cisplatin-treated rats revealed obvious pathological findings of marked depletion and degeneration of lymphoid tissue. Co-oral administration of Immulant resulted in substantial improvement of various immunotoxicological indices compared to cisplatin control.

Conclusion: The herbal medicine Immulant is an immunostimulant which could be used to treat the immunotoxic effects of cisplatin. Graphical abstract Cisplatin (CP) is a highly effective antineoplastic DNA alkylating agent. CP induces free radical production causing an oxidative damage.Cisplatin induced marked inhibition in cellular and humoral immunityEchinacea purpurea (Immulant) is a powerful anticytotoxic agent against cisplatin toxicity.

Keywords: Cisplatin; Echinacea purpurea; Immulant; Immunotoxicity; Rats.

Graphical abstract

Cisplatin (CP) is a highly effective antineoplastic DNA alkylating agent. CP induces free radical production causing an oxidative damage.Cisplatin induced marked inhibition in cellular and humoral immunityEchinacea purpurea (Immulant) is a powerful anticytotoxic agent against cisplatin toxicity.

Fig. 1

Histopathological findings on spleens from various experimental groups. a A section of spleen of the control group showing normal histological architecture into white (W) and red pulps (R) (H&E; ×100). b A section of spleen of the control group showing thin reticular fiber in the capsule (arrow) (Gomori’s reticulin; ×400). c A section of spleen of the control group showing white pulp (W) separated from red pulp (R) with well visible marginal zone (MZ) (H&E; ×400). d A section of spleen of the cisplatin-treated group showing disorganization of lymphoid follicles (H&E; ×400). e A section of spleen of the cisplatin-treated group showing depletion of lymphocytes in red pulp with edema (arrow), and some necrotic cells in white and red pulps (H&E; ×100). f A section of spleen of the cisplatin-treated group showing increasing of hemosiderosis, fibrosis (arrow) in the red pulp and some lymphoid follicles, dilated and congested blood vessels (BV) (Crossmon’s trichrome; ×400). g A section of spleen of the cisplatin-treated group showing thickening in the reticular fiber of the capsule and the trabeculae (Gomori’s reticulin; ×400). h A section of spleen of the cisplatin- and Immulant-treated group showing hypocellularity of the red pulp and germinal center (arrow). (H&E; ×100). i A section of spleen of the cisplatin- and Immulant-treated group showing depletion of periarterial lymphatic sheath (arrow). (H&E; ×100). j A section of spleen of the cisplatin- and Immulant-treated group showing decrease dilated and congested blood vessels (BV) and collagen fibers (arrow). (Crossmon’s trichrome; ×100). k A section of spleen of the Immulant-treated group showing white (W) and red pulps (R) (H&E; ×100)

Fig. 2

Immunohistochemical profile of caspase-3 expression in spleen in various experimental groups. a A section of spleen of the control group showing negative caspase-3 immunoreactivity (caspase-3; ×100). b A section of spleen of the cisplatin-treated group showing intense caspase-3 reaction expressed in white and red pulp (caspase-3; ×100). c A section of spleen of the cisplatin-treated group showing intense caspase-3 reaction expressed in white and red pulp (caspase-3; ×400). d A section of spleen of the cisplatin-and Immulant-treated group showing mild to negative caspase-3 immunohistochemical expression (caspase-3; ×100). e A section of spleen of the Immulant-treated group showing negative caspase-3 immunohistochemical expression (caspase-3; ×1000)