Curcumin Attenuates Radiation-Induced Inflammation and Fibrosis in Rat Lungs

Abstract

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-κ B (NF-κB) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review

“…Others act against radiation exposure by inducing the expression of Mn-SOD, GSH, CAT, and GPx, the important members of antioxidant defence system (Han et al, 2005;Gottfredsen et al, 2014) or modulate the immune response against radiation exposure Qiu et al, 2008;Pragya et al, 2014;Yu et al, 2014). Additionally, some of these plant extract/plant-derived compounds have also been found to reduce ROS, suppress cytokines, TNF-α and TGF-β1, thereby reducing the OH-proline level (the fibrotic index) in radiation-induced lung tissue (Han et al, 2006;Xie et al, 2006;Lee et al, 2009;Lee et al, 2010;Flechsig et al, 2010;Qiu et al, 2011;Gorshkova et al, 2012;Cho et al, 2013;Ding et al, 2013;Horton et al, 2013). Therefore, in general, the plant extracts/plant-derived compounds might act, either by suppressing some of these radiationinduced proinflammatory cytokines and other mediators of inflammatory response such as TNF-α, which in turn can induce the antioxidant defence system, or might activate the antioxidant defence system directly, in response to radiation exposure.…”

“…Agents that can be radioprotective must counter some or all the damaging effects of radiological exposure in the cell including those mentioned above. Radiation-induced inflammation, an important side effect that contributes to normal tissue injury, has been reported in many species (Linard et al, 2004;Fliedner et al, 2005;Kong et al, 2005;Fleckenstein et al, 2007;Haston et al, 2007;Rodemann and Blaese, 2007;Hill et al, 2011;Multhoff and Radons, 2012;Rastogi et al, 2012;Cho et al, 2013;Fu et al, 2013;Jiang et al, 2013;McCurdy et al, 2013;Moore et al, 2013;Mukherjee et al, 2014). The initial phase of radiationinduced injury is marked by the increase in the synthesis of pro-inflammatory cytokines such as transforming growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) and several other members of interleukin (IL) family (Linard et al, 2004;Fliedner et al, 2005;Kong et al, 2005;Mehta, 2005;Fleckenstein et al, 2007;Haston et al, 2007;Rodemann and Blaese 2007;Jindal et al, 2009;Hei et al, 2011;Janko et al, 2012;Monceau et al, 2013).…”

“…The initial phase of radiationinduced injury is marked by the increase in the synthesis of pro-inflammatory cytokines such as transforming growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) and several other members of interleukin (IL) family (Linard et al, 2004;Fliedner et al, 2005;Kong et al, 2005;Mehta, 2005;Fleckenstein et al, 2007;Haston et al, 2007;Rodemann and Blaese 2007;Jindal et al, 2009;Hei et al, 2011;Janko et al, 2012;Monceau et al, 2013). The hallmark late effect of radiation exposure in several experimental animals is fibrosis, which is often permanent (Han et al, 2006;Lee et al, 2009;Flechsig et al, 2010;Qiu et al, 2011;Gorshkova et al, 2012;Cho et al, 2013;Ding et al, 2013;Horton et al, 2013). A number of chemical agents showed mitigation to radiation-induced injuries in animal models (Gandhi and Nair, 2004;Parihar et al, 2007;Thotala et al, 2009;Brown et al, 2010;Gao et al, 2012;Kma et al, 2012;Peebles et al, 2012;Alok et al, 2013;Copp et al, 2013).…”

Drug therapy to prevent and diminish radiation injury of the lungs

“…По сравнению с контрольной группой, получавшей обычную диету и лучевую терапию, у животных от мечено уменьшение лучевого фиброза легких и по вышение выживаемости. В работе [49] выявлено, что при ежедневном внутрижелудочном введении кры сам в дозе 200 мг / кг в течение 1 нед. до однократ ного облучения грудной клетки и 8 нед.…”

Translating Curcumin to the Clinic for Lung Cancer Prevention: Evaluation of the Preclinical Evidence for Its Utility in Primary, Secondary, and Tertiary Prevention Strategies

“…Hamdy et al, 2012;Nemmar et al, 2012;Suresh et al, 2012;Xiao et al, 2012;Avasarala et al, 2013;Cho et al, 2013)] resulted in pulmonary edema, alveolar wall thickening, inflammatory cell infiltration, and fibrosis. These symptoms were attenuated by curcumin (most often delivered orally) at doses typically in the region of 50 mg/kg, which would equate to a dosing regimen of approximately 3.5 g/d for a 70 kg human.…”