Cyclophosphamide Side Effects

Ovarian cancer is a set of malignancies that start in the ovaries, as well as adjacent portions of the fallopian tubes and peritoneum. Women have two ovaries, one on each side of the uterus. The ovaries produce reproductive hormones and egg cells. Thousands of women each year get an ovarian cancer diagnosis and this type of cancer ranks fifth in cancer deaths among women.

Cyclophosphamide is an effective alkylating chemotherapy agent used to treat ovarian cancer. Although cyclophosphamide has many benefits cyclophosphamide-induced ovarian toxicity is a side effect of treatment with this drug. This type of toxicity can cause infertility and increase the risk of developing cancer in the ovaries. While there is no cure for this condition, there are treatments that can help lessen its symptoms.

Ovarian function and development are jeopardized by rapid depletion of the oocyte reserve, which is caused by apoptotic cell death and ovarian atrophy during cyclophosphamide treatment. In humans, rest primordial follicles and growing follicles disappear as a result of cyclophosphamide-induced ovarian toxicity.

The symptoms of cyclophosphamide-induced ovarian toxicity can vary from person to person, but may include:

• Infertility
• Increased risk of cancer in the ovaries
• Bloating
• Abdominal pain
• Nausea
  
• Vomiting

There are ways to reduce the risk of cyclophosphamide-induced ovarian toxicity happening. One is to limit the amount of cyclophosphamide that is taken. Another is to make sure that there is a period of rest after each dose. This will allow the ovaries to recover.

The antioxidant defense system is responsible for protecting the body from oxidative damage. This damage can occur as a result of exposure to environmental toxins such as cigarette smoke or as a side effect of certain medications such as cyclophosphamide. One way to protect the body from the harmful side effects of cyclophosphamide is to increase the intake of antioxidants.

Cyclophosphamide has been shown to have some toxicity towards normal cells, which is thought to be due to the generation of reactive oxygen species (ROS). ROS are unstable molecules that can damage cellular structures and DNA. Cyclophosphamide treatment has been shown to increase ROS levels and this may contribute to the drug's cytotoxicity. Additionally, ROS can activate certain pathways that promote cell death. Therefore, cyclophosphamide-induced ROS may play a role in the ability of the drug to kill cancer cells. Additional research is needed to determine the exact role of ROS in cyclophosphamide toxicity.

At present, it is known that cyclophosphamide interferes with the antioxidant system and increases ROS levels, which ultimately leads to lipid peroxidation, damage to the mitochondria and inflammation. These events then result in the activation of caspase members which cause ovarian follicle apoptosis.  

Cilostazol is a PDE-3 inhibitor drug that has been shown to be effective in reducing the toxicity side effects caused by cyclophosphamide. Cilostazol has been found to have additional pharmacological qualities such as antioxidant, anti-diabetic and anti-inflammatory effects. Cilostazol decreases lipid peroxidation; oxidative stress and tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL‐6), and IL‐1beta signaling pathways. As well as this, cilostazol aids in the overexpression of hemoxygenase-1 (HO-1) and it can inprove cyclophosphamide-induced ovarian damage via the cAMP pathway. (Aziz et al., 2020)