Cromoglycate, not ketotifen, ameliorated the injured effect of warm ischemia/reperfusion in rat liver: role of mast cell degranulation, oxidative stress, proinflammatory cytokine, and inducible nitric oxide synthase

Figures & data

Figure 1 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on ISCH/REP injury-induced changes in microscopic appearance of liver sections after hematoxylin and eosin staining (H&E ×100).

Notes: (A) SHAM, (B) 45 minutes following ISCH and 60 minutes following REP, (C) CROM + ISCH/REP, and (D) KET + ISCH/REP. (A) SHAM liver tissue showing within normal appearance. (B) ISCH/REP caused severe congestion and dilated vessels of portal tract and central veins with mild inflammatory reaction in portal tract. (C) CROM caused within the normal appearance of liver tissue. (D) KET caused a mild inflammatory reaction of portal tract and mild dilation and congestion of portal tract and central veins.
Abbreviations: ISCH/REP, ischemia/reperfusion; CV, central vein; PA, portal artery.

Table 1 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactic dehydrogenase (LDH) levels in rats subjected to ischemia/reperfusion (ISCH/REP)-induced injury

Groups	ALT (U/L)	AST (U/L)	LDH (U/L)
SHAM	43±11	137±62	769±299
ISCH/REP	671±200a	837±92a	1,393±529a
CROM	250±61b	627±122b	853±283b
KET	696±79	696±160	1,540±204

Notes: Data are the mean ± SD of six rats.

a Significantly different from the SHAM group (P≤0.05).

b Significantly different from the ISCH/REP group (P≤0.05).

Figure 2 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on liver lipid peroxide (MDA) concentration in rats subjected to ischemia/reperfusion (ISCH/REP)-induced injury. Each point represents the mean ± SD of six rats.

Notes: *Significantly different from the SHAM group (P≤0.05). ^#Significantly different from the ISCH/REP group (P≤0.05).
Abbreviation: MDA, malondialdehyde.

Figure 3 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on liver nitric oxide (NO) concentrations in rats subjected to ischemia/reperfusion (ISCH/REP)-induced injury. Each point represents the mean ± SD of six rats.

Notes: *Significantly different from the control group (P≤0.05). ^#Significantly different from the ISCH/REP group (P≤0.05).

Figure 4 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on reduced glutathione (GSH) content in the liver of rats subjected to ischemia/reperfusion (ISCH/REP)-induced injury. Each point represents the mean ± SD of six rats.

Notes: *Significantly different from the control group (P≤0.05). ^#Significantly different from the ISCH/REP group (P≤0.05).

Table 2 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on liver tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) concentrations in rats subjected to ischemia/reperfusion (ISCH/REP)-induced injury

Groups	TNF-α (pg/g tissue)	IL-6 (pg/g tissue)
SHAM	321±29	1,285±334
ISCH/REP	517±196a	1,845±249a
CROM	323±47b	1,434±262b
KET	288±59b	1,280±522b

Notes: Data are the mean ± SD of six rats.

a Significantly different from the SHAM group (P≤0.05).

b Significantly different from the ISCH/REP group (P≤0.05).

Figure 5 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on ISCH/REP-induced injury changes in mast cell recruitment and granulation in liver sections after toluidine blue staining: (A) SHAM; (B) 45 minutes following ISCH and 60 minutes following REP; (C) CROM + ISCH/REP; and (D) KET + ISCH/REP.

Notes: (A) The SHAM liver shows a relatively low number of granulated mast cells; (B) ISCH/REP liver shows increased drainage and degranulation of the mast cells; (C and D) CROM and KET livers show an increased number of heavily granulated mast cells. (E) The number of granulated mast cells is shown. *Significantly different from the control group (P≤0.05). ^#Significantly different from the ISCH/REP group (P≤0.05).
Abbreviation: ISCH/REP, ischemia/reperfusion.

Figure 6 Effect of sodium cromoglycate (CROM) and ketotifen (KET) on liver inducible nitric oxide synthase (iNOS) immunoreactivity examined in rats subjected to ischemia/reperfusion (ISCH/REP) injury: (A) rat liver under control conditions (SHAM); (B) 45 minutes following ISCH and 60 minutes following REP; (C) CROM + ISCH/REP; and (D) KET + ISCH/REP.

Notes: Negative (−) iNOS immunoreactivity can be detected in the liver shown in (A) and (C). Moderate positive (++) iNOS immunoreactivity (brown staining) can be detected in the liver shown in (B). Severe positive (+++) iNOS immunoreactivity (brown staining) can be detected in the liver shown in (D). Histogram (E) shows a significant increase in immunoexpression of iNOS in the liver of ISCH/REP rats compared with that of the control rats and in that of KET rats compared with those of ISCH/REP rats. The arrows show iNOS expression. *Significantly different from the control group (P≤0.05). ^#Significantly different from the ISCH/REP group (P≤0.05).