Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress.

 

J Oral Sci. 2010;52(2):251–6.

 

Oral cancer being the sixth most common cancer has shown its prevalence in Asian countries, in particular in India due to smoking and alcohol intake habits. In India, WHO has estimated that 90% of oral cancers are due to the use of tobacco for chewing and smoking.

Exposure to carcinogens leads to genetic, epigenetic and metabolic changes, which lead to development of oral squamous cell carcinoma. About 8–10 % of the pre-cancerous lesions like oral leukoplakia and submucous fibrosis can turn malignant. Histopathological diagnosis can be used for confirming presence of epithelial dysplasia in such cases. However, not all the lesions that show dysplasia will become malignant and those lesions which did not show epithelial dysplasia during biopsies may even develop carcinoma.

In the previously published literature presence, salivary lipid peroxidation products like malonaldehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) have been seen in oral cancer. Decrease of antioxidant activity and use of supplementation with antioxidants like vitamins C and E have been linked with health benefits.

Curcumin (diferuloylmethane), the yellow coloring agent of turmeric, is known for its antioxidant property. In many research articles it has been used as a chemopreventive agent in various types of cancers. Curcumin has also been shown to downregulate smokeless tobacco extract (Khaini) or nitrosamine, 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK)-induced NF-KappaB and COX-2 in oral premalignant and cancerous cell in vitro.

 

Objective

To test the effect of curcumin in patients with leukoplakia, oral submucous fibrosis and lichen planus by measuring serum and salivary levels of MDA, 8-OHdG and Vitamin C, E before and after curcuminoids administration.

 

Study Design:

Four groups of subjects: a) with oral leukoplakia (n=25), b) with oral submucous fibrosis (n=25), c) with oral lichen planus (OLP, n=25) and d) healthy individuals (n=25) aged 17–50 years with no systemic, chronic, dental diseases and smoking/alcohol/drug history were selected for the study. The intervention used in study was 1 g caplet having 1000 mg of total curcuminoids (900 mg curcumin, 80 mg demethoxycurcumin and 20 mg of bisdemethoxycurcumin) manufactured by Sabinsa Corporation. Salivary and serum level of MDA, 8-OHdG and vitamin C and E were measured before the intake of intervention, one week after the intake and following clinical cure of lesions. In the study, two main variables for assessing cure of oral leukoplakia, OLP and oral submucous fibrosis were pain control and lesion healing.

 

Results and Discussion:

  1. In case of subjects with oral leukoplakia, submucous fibrosis and OLP the mean and median value of serum and salivary vitamin C & E was increased, whereas levels of MDA and 8-OHdG were decreased after one week of intake of intervention as compared to baseline
  2. After clinical cure of the disease, above values were found to be clinically significant (p<0.05)
  3. Pain score and size of lesion improved significantly in case of subjects with oral leukoplakia, submucous fibrosis and OLP (p<0.05)
  4. In case of subjects with submucous fibrosis, mouth opening recovered significantly (p<0.05)
  5. Subjects from groups oral leukoplakia (15), submucous fibrosis (17) and OLP (18) were clinically cured after 131, 211 and 191 days, respectively
  6. After clinical curing of lesion, the values of serum and salivary vitamin C and E showed decrease as compared to healthy individuals, it increased in all groups following curcuminoids regimen
  7. Similarly, after clinical cure of lesion, values of serum MDA and 8-OHdG were increased in each group as compared to healthy individuals but significantly decrease in each group

 

Conclusion:

The study suggests that in subjects with precancerous lesions, curcuminoids supplementation significantly increased the systemic, local antioxidant status and vitamin C and E levels. Levels of lipid peroxidation products, MDA and 8-OHdg were found to be lowered. Authors also suggested that this effect is mediated via pro-oxidant and antioxidant pathway. On the safety part, curcuminoids supplementation was safe up to 8 g/day with no treatment-related toxic effects in the subjects. The study also suggested the importance of measurement of salivary biomarkers in early detection of oral cancer risk.

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Sabinsa Corporation is a manufacturer, supplier and marketer of herbal extracts, cosmeceuticals, minerals, dietary supplements and specialty fine chemicals for the nutritional, cosmetic, pharmaceutical and food industries.

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