Bleomycin sulfate: Chemical property and Biological function

Introduction

Bleomycin sulfate is a cytotoxic sulfur-containing polypeptide mixture of glycoproteins that can be separated by chromatography into two main fractions: bleomycin A and B. These fractions can be further separated into the subfractions bleomycin A1-6 and B1-5. Of these, A2 and B2 are the main components of commercially available bleomycin[1].

Bleomycin was first isolated from the soil fungus Streptomyces verticellus in 1969, and it was found to have antibacterial, antitumoral, and antiviral properties. Since its discovery, bleomycin has been used systemically as a single agent and in combination for the treatment of various neoplasms, including lymphoma, squamous cell carcinoma, and testicular carcinoma. Its effects occur through the inhibition of DNA synthesis and the lesser inhibition of RNA and protein synthesis. Systemic bleomycin alters DNA metabolism by causing strand scission and elimination of purine and pyrimidine bases. The antibiotic also can cleave RNA to a lesser degree and in a more highly selective fashion. It also acts as an inducer and regulator of apoptosis in various cells and inhibits tumour angiogenesis.

Chemical property

Bleomycin sulfate is an antineoplastic antibiotic, a purified mixture of glycopeptides produced by a fermentation process employing the actinomycetes Streptoverticillium species. The bleomycin mixture contains predominantly the A2 and B2 peptides. Bleomycin sulfate is a white, yellowish-white, or cream-coloured amorphous hygroscopic powder. It is soluble in water, slightly in dehydrated alcohol, and practically insoluble in acetone and ether. DBL Bleomycin Sulfate for Injection is a white to cream-coloured lyophilised powder or plug. When reconstituted in Water for Injection, the pH of the solution is approximately 5.

Biological function

Bleomycin sulfate is a sclerosing antibiotic with antineoplastic efficacy. It shows antineoplastic efficacy by inhibiting deoxyribonucleic acid (DNA) synthesis and, less frequently, RNA and protein synthesis. It is used for chemotherapeutic purposes in Hodgkin lymphoma, squamous cell carcinoma, lymphoma, and germ cell tumors. When administered via systemic route, bleomycin sulfate causes secretion of tumor necrosis factor (TNF)-α in particular, as well as interleukin (IL)-1β, IL-8, and transforming growth factor (TGF)-β, from inflammatory cells in human and animal lungs. Although the pathogenesis of bleomycin-induced pulmonary fibrosis is not understood exactly, TGF-β is considered an important cytokine associated with fibroblast proliferation and collagen synthesis, and TNF-α is considered a central mediator in bleomycin-induced pulmonary fibrosis. When applied locally, bleomycin acts as an irritating agent and initiates an inflammatory process. It activates inflammatory cells by stimulating cytokine synthesis; it also stimulates fibroblast proliferation and enhances collagen synthesis[2].

Side effects

Bleomycin sulfate is a sclerosing antibiotic with antineoplastic efficacy. One of the adverse effects of bleomycin is lung fibrosis, which is a potentially fatal complication that can develop during systemic use. The local sclerosing adhesive effect of bleomycin results from extreme inflammatory stimulation and fibrosis, which occurs locally in the application area. For this purpose, intrapleurally application in the treatment of pleural effusion was reported with 31% and 85% success rate. Some sclerosing agents have been used to treat seroma formation after breast cancer surgery, and it was reported that they reduced seroma formation to some extent.

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