Letter to Editor on: "Ginger (Zingiber officinale roscoe) extract could upregulate the renal expression of NRF2 and TNFα and prevents ethanol-induced toxicity in rat kidney" by Akbari et al.

Document Type : Letter to Editor

Authors

Department of Pharmacology, The Gold lab, Molecular Medicine and Toxicology Division, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India

Abstract

A recent study entitled “Ginger
(Zingiber officinale roscoe) extract
could upregulate the renal expression
of Nrf2 and TNFα and prevents
ethanol-induced toxicity in rat kidney”
that was published in this journal by
Fathi et al., 2021) states that ethanol
can activate Nrf2 expression. Nuclear
factor E2-related factor (Nrf2)
regulates the expression of a variety of
genes responsible for intracellular
detoxification, and antioxidant, antiinflammation, anti-stress activities, etc
(Ezhilarasan et al., 2016). Nrf2 is
crucial for the induction of endogenous
antioxidant enzymes such as heme
oxygenase 1 and reduced glutathione
via activation of intracellular antioxidant
responsive element. Therefore, activation
of Nrf2 pathway by phytochemicals has been
demonstrated to provide protection against
alcohol-related abnormalities suggesting the
beneficial role of Nrf2 activation (Zhao et
al., 2018; Ezhilarasan et al., 2016). Besides,
a growing body of evidence reports the
protective role of Nrf2 against a number of
kidney diseases (Hejazian et al., 2021). Nrf2
activates several intracellular antioxidant
enzymes during the onset of intracellular
oxidative stress (Ezhilarasan, 2018).
Therefore, Nrf-2 activation is usually
considered to have a beneficial effect.
Previous studies also showed that ethanol
administrations can downregulate or
suppress Nrf-2 expression (Sueblinvong et
al., 2014; Shanmugam et al., 2019). In view
of the above scenario, as a powerful
oxidative agent, how ethanol could activate
Nrf2 expression? The authors have showed
that ginger, ethanol and ethanol+ginger
treatments can activate Nrf2 expression. The
manuscript was also failed to discuss about
the reason behind Nrf2 upregulation after
ethanol administration. These discrepancies
must be addressed in the discussion part.
The objectives of the study were
interesting, however, there were some
discrepancies in the title and their results
furnished. Therefore, we wish to seek your
attention towards this publication. The main
concern of this publication is the title. The
title says “Ginger (Zingiber officinale
Elumalai et al.
 AJP, Vol. 13, No. 1, Jan-Feb 2023 2
roscoe) extract could upregulate the
renal expression of Nrf-2 and tumor
necrosis factor alpha (TNF-α) and
prevents ethanol-induced toxicity in rat
kidney”. However, in results the
authors were reported that Ginger can
downregulate ethanol-induced TNF-α.
Moreover, as reported in the title Ginger
extract did not ameliorate ethanol-induced
Nrf-2 downregulation. 

Keywords


Ezhilarasan D, Evraerts J, Brice S, BucCalderon P, Karthikeyan S, Sokal E,
Najimi M. 2016. Silibinin inhibits
proliferation and migration of human
hepatic stellate LX-2 cells. J Clin Exp
Hepatol, 6: 167-174.
Ezhilarasan D. 2018. Oxidative stress is bane in
chronic liver diseases: Clinical and
experimental perspective. Arab J
Gastroenterol, 19: 56-64.
Hejazian SM, Hosseiniyan Khatibi SM,
Barzegari A, Pavon-Djavid G, Razi
Soofiyani S, Hassannejhad S, Ahmadian
E, Ardalan M, Zununi Vahed S. 2021. Nrf2 as a therapeutic target in acute kidney
injury. Life Sci, 264: 118581.
Li JP, Gao Y, Chu SF, Zhang Z, Xia CY, Mou
Z, Song XY, He WB, Guo XF, Chen NH.
2014. Nrf2 pathway activation contributes
to anti-fibrosis effects of ginsenoside Rg1
in a rat model of alcohol- and CCl4-
induced hepatic fibrosis. Acta Pharmacol
Sin, 35: 1031-1044.
Robledinos-Antón N, Fernández-Ginés R,
Manda G, Cuadrado A. 2019. Activators
and inhibitors of NRF2: A review of their
potential for clinical development. Oxid
Med Cell Longev, 2019: 9372182.
Shanmugam S, Patel D, Wolpert JM, Keshvani
C, Liu X, Bergeson SE, Kidambi S,
Mahimainathan L, Henderson GI,
Narasimhan M. 2019. Ethanol impairs
NRF2/antioxidant and growth signaling in
the intact placenta in vivo and in human
trophoblasts. Biomolecules 9: 669.
Sueblinvong V, Tseng V, Smith T, Saghafi R,
Mills ST, Neujahr DC, Guidot DM. 2014.
TGFβ1 mediates alcohol-induced Nrf2
suppression in lung fibroblasts. Alcohol
Clin Exp Res, 38: 2731-2742.
Zhao N, Guo FF, Xie KQ, Zeng T. 2018.
Targeting Nrf-2 is a promising
intervention approach for the prevention of
ethanol-induced liver disease. Cell Mol
Life Sci 75: 3143-3157