Low-power laser irradiation fails to improve liver regeneration in elderly rats at 48 h after 70 % resection

Abstract

The liver regeneration is an important clinical issue after major hepatectomies. Unfortunately, many organs (including the liver) exhibit age-related impairments regarding their regenerative capacity. Recent studies found that low-power laser irradiation (LPLI) has a stimulatory effect on the liver regeneration process. However, its effects in elderly remain unknown. Thus, this study aimed to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized elderly rats exposed to LPLI. The effects of 15 min of LPLI (wavelength of 632.8 nm; fluence of 0.97 J/cm(2); total energy delivered of 3.6 J) were evaluated in hepatectomized elderly Wistar male rats. Afterwards, through immunoblotting approaches, the protein expression and phosphorylation levels of hepatocyte growth factor (HGF), Met, Akt and Erk 1/2 signaling pathways as well as the proliferating cell nuclear antigen (PCNA) were investigated. It was observed that LPLI was not able to improve liver regeneration in elderly rats as evidenced by the lack of improvement of HGF and PCNA protein expression or phosphorylation levels of Met, Akt and Erk 1/2 in the remnant livers. In sum, this study demonstrated that the main molecular pathway, i.e. HGF/Met → Akt and Erk 1/2 → PCNA, involved in the hepatic regeneration process was not improved by LPLI in elderly hepatectomized rats, which in turn rules out LPLI as an adjuvant therapy, as observed in this protocol of liver regeneration evaluation (i.e. at 48 h after 70 % resection), in elderly.

Low-Power Laser Irradiation (LPLI): A Clinical Point of View on a Promising Strategy to Improve Liver Regeneration

“…Also, we did not observe any significant improvement in HGF and PCNA protein expression. 23 Taken together, the results of this study indicate that LPLI cannot induce any improvement in the hepatic regeneration process for at least 48 hours after 70% resection, which excludes LPLI as an auxiliary therapy in elderly hepatectomized rats. 23…”

“…These images was based from previous studies. 21,23 involved in the regenerative effect of the laser in various tissues. 12,14 This data led us to hypothesize the effect of the laser on the regenerative molecular pathway HGF → Met→ Akt and Erk 1/2.…”

Effects of Low-Level Laser Therapy on Liver Regeneration and the Laser Parameters Employed

“…Nine studies were found matching the study criteria. All studies were performed in rats who underwent PH, seven studies realized a 70% PH (ARAÚJO et al, 2013;ARAÚJO et al, 2014;BARBOSA et al, 2011;CASTRO-SILVA et al, 2001;CASTRO-SILVA et al, 2003;GODOY et al, 2017;ORON et al, 2010), one 67% PH (MELO et al, 2005) and the other 90% PH (OLIVEIRA et al, In order to evaluate the regenerative effects of LLLT in partial hepatectomized rats, the studies evaluated biological parameters as respiratory activity of the mitochondria, phosphorylative activity of the liver (BARBOSA et al, 2011;CASTRO-SILVA et al, 2001;CASTRO-SILVA et al, 2003;MELO et al, 2005), mitochondrial membrane potential (BARBOSA et al, 2011;MELO et al, 2005), cell proliferation through proliferating cell nuclear antigen (PCNA) (ARAÚJO et al, 2013;ARAÚJO et al, 2014;CASTRO-SILVA et al, 2003;MELO et al, 2005;OLIVEIRA et al, 2006) or Ki-67 (ARAÚJO et al, 2013;ARAÚJO et al, 2014) labeling index, and liver damage through the measurement of serum aminotransferase level (CASTRO-SILVA et al, 2001;GODOY et al, 2017;MELO et al, 2005;OLIVEIRA et al, 2006).…”

“…In one study, 5-bromine-2'-desoxyuridine (BrdU) was applied in order to analyze cell proliferation and angiogenesis through immunohistochemical marking (OLIVEIRA et al, 2006). The activation or expression of specific proteins like hepatocyte growth factor (HGF), HGF receptor (MET), protein kinase B (AKT), and protein kinases activated by mitogens (MAPK) were also evaluated to investigate signaling pathways involved in the LLLT mechanism of action (ARAÚJO et al, 2013;ARAÚJO et al, 2014).…”

“…Studies about the effect of LLLT on liver regeneration after PH on experimental animals suggest effectiveness, but there are differences in the methodology and the laser parameters are not clear (ARAÚJO et al, 2013;ARAÚJO et al, 2014;BARBOSA et al, 2011;GODOY et al, 2017;CASTRO-SILVA et al, 2001;CASTRO-SILVA et al, 2003;MELO et al, 2005;ORON et al, 2010;OLIVEIRA et al, 2006). Considering the therapeutic potential of LLLT, the aim of this article was to review the recent studies on the effects of LLLT on rat healthy liver regeneration after PH and the laser parameters employed.…”