Lead (Pb), a threat to protein metabolic efficacy of liver, kidney and muscle in mice

Abstract

Lead, being the most dangerous natural heavy metal imposes metabolic dysfunction in organ system. However, the effect of lead on protein metabolic efficacy in the liver, kidney and skeletal muscle in mice has not been well studied. The aim of the present study is to establish the metabolic orientation between the liver, kidney and muscle upon subacute lead exposure to assess how protein and amino acid metabolisms are affected. Lead acetate was administered by gavage at a dose of 5 mg/kg b.w./once daily for 30 days. After the treatment, the liver, kidney and muscle were evaluated for biochemical parameters such as proteolytic enzyme activities (trypsin, cathepsin and pronase), tissue protein content (acidic, basic, neutral and total protein), protein carbonyl content, free amino nitrogen as well as tissue and serum transaminase activities. Degradation of total protein was noted in the liver and kidney possibly due to enhanced carbonylation of proteins whereas it was elevated in skeletal muscle. The proteolytic enzyme activity was inhibited in the liver and elevated in the kidney by lead treatment. Muscular cathepsin and trypsin activities decreased but the pronase activity enhanced following lead exposure. Moreover, a marked reduction of transaminase enzyme activities in all the tissues might be due to enzyme leakage from tissue to blood. Significant alteration in amino acid nitrogen in the affected tissue indicates adaptive mechanisms at play in the organ system. Lead is found to be responsible for alteration of tissue protein and amino acids in a toxic fashion and promotes a cooperative mechanism to minimize the metabolic distress imposed by lead.

Metabolic adaptability in liver and gastrocnemius muscle of mice following subacute lead toxicity

“…This booster effect of ROS produced by NADPH may surely disturb the cell membrane as well as cellular protein content. Additionally, enhancement of protein carbonyl content in the liver and skeletal muscle as found in our earlier study (Das and Pal, 2017b) is supportive in relation to ROS production by Pb that might be influenced by increased NADPH oxidase activity.…”

“…So, there may be a cooperative manifestation by which the basic proteins of skeletal muscle may be engaged in forming those binding sites to enhance the enzyme activity through interaction with more substrates. It is supported by our earlier studies (Das and Pal, 2017b) where basic protein depletion was an important factor of Pb toxicity. Current investigation further shows significant enhancement of the NADPH oxidase activity in the affected tissues.…”

“…Accumulation of Pb leads to toxic manifestations at the cellular level like production of oxidized DNA, alterations in protein and lipid metabolism showing a strong correlation between Pb toxicity and metabolic variation (Patra and Swarup, 2004). Pb-induced change in tissue protein metabolism has already been observed previously in relation to tissue Pb deposition (Das and Pal, 2017b).…”

“…Pb being a toxic heavy metal causes metabolic stress by alteration of different metabolic parameters like acid and alkaline phosphatases, lactate dehydrogenase (LDH), transaminase, and serum lipid profiles to which toxicity and organ dysfunctions may be attributed (Allouche et al, 2011). Moreover, Pb-induced alteration in protein metabolic efficacy in liver, kidney, and skeletal muscle was noted in our piror observations (Das and Pal, 2017b). Pb has adverse effects on the metabolic pathway of heme synthesis; certain physiological processes as well may cause hormonal imbalance and carcinogenesis (Singh et al, 2018).…”

“…The mice were supplied with a standard protein diet prepared by 18% casein, 9% fat, and 71% amylum along with vitamins and minerals used in earlier experiments (Das and Pal, 2017a, b). Drinking water was supplied ad libitum, and the animals were kept in the treatment room maintaining the room temperature at 22–25°C and humidity at 50% with alternative light and dark cycle for 12 h.…”